bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin expression on colorectal tumor cells growing as monolayers, as multicellular tumor spheroids, or in nude mice
Authors: Hauptmann Steffen , Denkert Carsten , Löhrke Heinz , Tietze Lothar , Ott Stephan , Klosterhalfen Bernd , Mittermayer Christian 
Published: February 2007

AbstractIn this study we compared the expression of integrin alpha chains 2, 3, 4, 5, 6, v and the beta chains 1, 3, 4 in 2 colorectal carcinoma cell lines (HRT‐18 and CX‐2), growing in confluent and subconfluent monolayer cultures, as multicellular tumor spheroids and in nude mice, using the immunofluorescence technique (confocal microscopy) and flow cytometry. The fast‐growing cell line HRT‐18 expressed, in confluent and subconfluent monolayer cultures, alpha 2, 3 and beta 1 with a continuous membranous staining pattern, whereas alpha v, alpha 6, and beta 4 were expressed continuously membranous in the intermediate and apical part of the cell layer, and clustered at focal contacts at the base of the cells. In spheroids and tumors of nude mice the focal pattern of alpha v, 6 and beta 4 was changed into a diffuse one. Using flow cytometry, the expression of alpha 3 was found to be reduced in spheroids of HRT‐18. The slowly‐growing cell line CX‐2 expressed, under the same conditions in monolayer culture, alpha 6, beta 1 and beta 4, and very weakly alpha 2, 3, 5 and v. Alpha 3 was expressed in spheroids of CX‐2 only at the outer rim where the cells proliferate. In contrast, alpha 2 and 5 were expressed mainly in the quiescent, non‐proliferating area. Alpha 6 was reduced in spheroids of CX‐2. In the nude mouse tumor of CX‐2, alpha 5 was expressed only focally and very weakly, alpha 2 was no longer detectable, but alpha v appeared to be enhanced in a focal pattern. These data indicate that integrin expression of tumor cells depends upon the culture system and that integrin expression in multicellular tumor spheroids is more similar to the in vivo situation in nude mouse tumors. © 1995 Wiley‐Liss, Inc.
Suramin sodium: Pronounced effects on methotrexate transport and anti‐folate activity in cultured tumor cells
Authors: Rideout Darryl C. , Bustamante Andres , Patel Rena , Henderson Gary B. 
Published: February 2007

AbstractSuramin is an experimental anti‐neoplastic agent which has shown promising activity against prostatic carcinoma and lymphoma in clinical trials. To elucidate its mechanism of action, suramin was examined for an effect on the transport of folate compounds by tumor cells. Influx of the anti‐folate methotrex‐ate via the reduced‐folate carrier system of CCRF‐CEM cells was found to be highly sensitive to inhibition by suramin but not to various other arylsulfonic acids. Inhibition by suramin was competitive, and the inhibition constant Ki was 1.3 μM, a value 3‐fold lower than the Kt for half‐maximal influx of methotrexate. Folate binding to the membrane‐associated folate‐binding protein of KB cells was not affected by suramin. Growth studies revealed that the response of human CCRF‐CEM, KB, PC‐3 and MCF‐7 cells to methotrexate was antagonized from 6‐ to 17‐fold by pharmacological levels (10–200 μM) of suramin. Conversely, growth inhibition was additive or synergistic when suramin was combined with metoprine, a lipophilic anti‐folate which enters cells by diffusion. Synergism was observed between metoprine and suramin in CCRF‐CEM cells, which take up folate exclusively through the reduced‐folate carrier (inhibitable by suramin), whereas additivity was observed for KB cells, which rely largely on the folate‐binding protein (unaffected by suramin) for folate import. Our results indicate that inhibition of cellular transport of folate compounds may explain part of the anti‐neoplastic effects of suramin on tumor cells. © 1995 Wiley‐Liss, Inc.
Circumvention of confluence‐dependent resistance in a human multi‐drug‐resistant colon‐cancer cell line
Authors: Garrido Carmen , Chauffert Bruno , Pinard Dominique , Tibaut Florence , Genne Philippe , Assem Mahfoud , Dimanche‐Boitrel Marie‐Thérèse 
Published: February 2007

AbstractColorectal adenocarcinomas are inherently resistant to anthracyclines and other topoisomerase‐II inhibitors. Resistance to doxorubicin of colon cancer cells (Caco2) depends on 2 main mechanisms. The first is typical multi‐drug resistance, characterized by the mdr1 gene and its product the P170 membrane glycoprotein. P170 effluxes anthracyclines out of cancer cells and is antagonized in vitro by verapamil. The second mechanism, which develops when cell‐culture density increases, we have designated confluence‐dependent resistance. Confluence‐dependent resistance depends on the reduced topoisomerase II content of the G0/G1,‐phase cells which accumulate in the confluent population. We show here that short treatments of confluent Caco2 cells with slightly toxic concentrations of DNA‐damaging agents (cisplatin, melphalan or mitomycin C) produced a transient accumulation of cells in S‐ and G2/M‐phases of the cell cycle. Concomitantly with the increase in the S‐phase population, the topoisomerase II cellular level and the sensitivity of cells to doxorubicin were greatly enhanced. Over‐coming confluence‐dependent resistance through S‐phase accumulation and inhibition of multi‐drug resistance by verapamil were fully additive, and a nearly complete reversal of confluent Caco2 cells' resistance to doxorubicin was obtained when both strategies were combined. © 1995 Wiley‐Liss, Inc.
Mouse embryo fibroblasts transformed by activated ras or dominant‐negative p53 express cross‐reactive tumor rejection antigens
Authors: Appleman Leonard J. , Uyeki James , Frey Alan B. 
Published: February 2007

AbstractTo study the immune response against oncogene‐trans‐formed tumors, C3H/HeN mouse embryo fibroblasts (MEF) were transfected with an activated allele of the H‐ras proto‐oncogene Val12 and a dominant‐negative allele of the murine p53 tumor suppressor gene Val135. Transformed cell lines were derived and found to be tumorigenic in syngeneic mice. Immunization with irradiated p53 + ras‐transformed MEF, but not primary MEF or unrelated syngeneic cells, protected mice from subsequent challenge with live tumor cells. The role of different immune cell subsets in the effector phase of anti‐tumor immunity induced by immunization with p53 + ras‐transformed MEF was investigated by in vivo antibody depletion experiments. Immunized mice depleted of CD8+ T, NK or B cells were resistant, but depletion of CD4+ T cells rendered mice susceptible to tumorigenic challenge. In contrast to the tumor‐specific immune responses mounted against most chemically or UV‐induced tumors, a series of independently derived p53 + ras‐transformed MEF were cross‐reactive in tumor rejection assays. In addition, immunization with C3H‐derived L‐929 cell lines expressing single gene products H‐ras or p53 did not protect mice against tumorigenic challenge with p53 + ras‐transformed tumors. However, MEF transformed by expression of either H‐ras or p53 were cross‐protective in vivo. Our data suggest that the p53 + ras‐transformed MEF share tumor rejection antigens which are also induced by single gene transformation of the parental primary cell but are not the products of oncogenic ras or p53 protein. © 1995 Wiley‐Liss, Inc.
Analgesics and cancers of the renal pelvis and ureter
Authors: Linet Martha S. , Chow Wong‐Ho , McLaughlin Joseph K. , Wacholder Sholom , Yu Mimi C. , Schoenberg Janet B. , Lynch Charles , Fraumeni Joseph F. 
Published: February 2007

AbstractTo evaluate renal pelvis and ureter (RPU) cancer risk in relation to lifetime use of analgesics, a population‐based case‐control study was carried out in 3 areas of the United States. Among 502 cases and 496 controls diagnosed and interviewed during 1983–1986, no significant increases in risk were found for any of the non‐prescription and prescription analgesics evaluated or among regular users of phenacetin, acetaminophen or aspirin. Neither cumulative lifetime ingestion nor duration of regular use of these 3 drugs, whether alone or in combination, was associated with significantly increased risk of RPU cancer, although a slight excess was observed among long‐term users of acetaminophen. Risk was not increased among persons reporting highest cumulative dose and/or longest duration of phenacetin use. Although our study of RPU cancer is the largest to date, it was nonetheless limited by the small number of regular analgesic users and the relatively low response rates. Because of the relatively recent onset of widespread use of acetaminophen, its pharmacologic similarity to phenacetin, a known urothelial carcinogen, and the elevation in risk seen in long‐term users, further surveillance of this analgesic is warranted. © 1995 Wiley‐Liss Inc.
Mechanisms of allele‐selective down‐regulation of HLA class I in Burkitt's lymphoma
Authors: Imreh Marta P. , Zhang Qian‐Jin , De Campos‐Lima Pedro O. , Imreh Stephan , Krausa Peter , Browning Michael , Klein George , Masucci Maria G. 
Published: February 2007

AbstractBurkitt lymphomas (BL) that arise in HLA‐A11‐positive individuals are characterized by selective loss/down‐regulation of the HLA AII polypeptide. We have investigated the molecular basis of such down‐regulation by comparing 5 pairs of BL lines and Epstein‐Barr virus (EBV)‐transformed lymphoblastoid cell lines (LCL) derived from the normal B cells of the same individuals. The presence of apparently intact HLA A11 genes was confirmed in all 5 BL/LCL pairs by polymerase chain reaction (PCR) typing and by Southern‐blot hybridization with HLA A locus‐specific probes. Northern‐blot analysis with locus‐and allele‐specific probes revealed a significantly lower expression or absence of A11‐specific mRNA in all 5 BL lines compared to the corresponding LCLs. Up‐regulation of Al1 ‐specific mRNA was achieved by IFNα treatment of 2 BL lines with low HLA A11 expression (BL‐28 and BL‐72) while the treatment had no effect in 3 BL fines (WWI ‐BL, WW2‐BL and BL41) that did not express the endogenous gene. HLA A11 expression was restored by transfection of the gene in WWI‐BL whereas transfectants of BL‐41 remained Al1‐negative. An HLA‐A11‐promoter‐driven chloramphenicol acetyl transferase reporter gene (pAl1 CAT) was active in WWI‐BL but not in BL‐41. HLA‐A11 was expressed in hybrids of BL‐41 with an A11‐positive LCL, while expression of the endogenous HLA A11 gene could not be restored by fusion of BL‐41 with an A11 ‐negative LCL, although an adequate set of transcription factors was present in the hybrid. Our results suggest that genetic defects and lack of transcription factors may contribute to the selective downregulation of HLA A11 in BL cells. © 1995 Wiley‐Liss Inc.
Hereditary aspects of endometrial adenocarcinoma
Authors: Suomi Raila , Hakala‐Ala‐Pietilä Tiina , Leminen Arto , Mecklin Jukka‐Pekka , Lehtovirta Pentti 
Published: February 2007

AbstractThe importance of heredity in the etiology of endometrial cancer (EC) was examined in a series of 326 patients with EC diagnosed at age 60 years or less. If one or both of the proband's parents had died of cancer, a thorough family history of malignancies was studied. Altogether 291 cases with complete parental data were found. Nine kindred (3.1%) showed features compatible with the dominantly inherited cancer trait known as hereditary non‐polyposis colorectal cancer (HNPCC). In another 9 cases, clustering of malignancies in 2 or more successive generations was indicative of familial cancer. A specific cancer aggregates were found in 112 probands' families, and family history was negative in 161 cases. No families had gynecological cancer as the only malignancy. HNPCC, the genetic etiology of which was recently revealed, seems to be an important risk factor for EC, indicating the significance of family‐history investigations of all patients with EC. Colorectal carcinoma (CRC) was here associated with EC also in families with clusterings of malignancies, but in these families no typical features of any known hereditary cancer syndrome could be found. On the basis of the results of the present study, proper surveillance for colorectal cancer should be recommended for patients with endometrial carcinoma if they belong to a family with features indicative of HNPCC. Furthermore, healthy gene carriers in an HNPCC family also need careful surveillance for CRC, EC and perhaps for other extra‐cofonic malignancies typical for HNPCC. Prophylactic surgery should even be considered in these cases. © 1995 Wiley‐Liss, Inc.
Age as a prognostic factor in breast cancer: Relationship to pathologic and biologic features
Authors: Bonnier Pascal , Romain Sylvie , Charpin Colette , Lejeune Christiane , Tubiana Nicole , Martin Pierre‐Marie , Piana Lucien 
Published: February 2007

AbstractThe relationship of age with prognostic factors and outcome of breast cancer has long been controversial due to numerous confounding factors. In order to clarify the prognostic value of age, we analyzed a homogeneous population of 1,266 patients treated for breast cancer at the same institution (mean follow‐up: 62 months). Three groups were compared: patients under 35 years of age, non‐menopausal patients over 35 years of age, and post‐menopausal patients under the age of 70 years. A higher frequency of undifferentiated tumors, histoprognostic grade‐3 cancer, microscopic lymph‐node involvement and negative hormonal receptor status was observed in patients under 35 years. In addition, clinical but not anatomical tumor size was greater in young patients, suggesting higher stromal activity. Metastasis‐free survival and overall survival were significantly poorer before 35 years. Differences were observed when patients were matched with regard to stage, anatomic size, histoprognostic grade, microscopic lymph‐node involvement and receptor status. Multivariate analysis of both overall and metastasis‐free survival demonstrated that age younger than 35 years was an independent risk factor. Younger women had a higher risk of local recurrence but, unlike older women, they did not experience any worsening of the already unfavorable outcome due to recurrence. © 7995 Wiley‐Liss, Inc.
EGFR gene amplification ‐ rearrangement in human glioblastomas
Authors: Schwechheimer Karl , Huang Su , Cavenee Webster K. 
Published: February 2007

AbstractImmunostaining using an affinity‐purified rabbit polyclonal antibody against the extracellular domain of the epidermal‐growth‐factor receptor (EGFR) showed over‐expression occurring in a fraction of tumor cells in 17 out of 18 human glioblastomas and in a majority of cells in 7 of the 18. Southern‐blotting technique using a full‐length EGFR cDNA probe showed a variable degree of amplification in 10 of the 17 glioblastomas, which was associated with EGFR over‐expression in each case. In 2 of the glioblastomas with EGFR gene amplification, a rearrangement of the gene affecting the extracellular domain of the receptor was identified and DNA sequence analyses revealed an identical deletion‐rearrangement of 801 base pairs between exons 2 to 7, resulting in an in‐frame fusion of exons I and 8. © 1995 Wiley‐Liss, Inc.
Comparison of cell‐cycle phase perturbations induced by the DNA‐minor‐groove alkylator tallimustine and by melphalan in the SW626 cell line
Authors: Erba E. , Mascellani E. , Pifferi A. , D'Incalci M. 
Published: February 2007

AbstractTallimustine or N‐deformyl‐N‐[4‐N‐N,N‐bis(2‐chloroethylamino)benzoyl], a distamycin‐A derivative (FCE 24517), is a novel anti‐cancer agent which alkylates N3 adenine in the minor groove of DNA. The cell‐cycle phase perturbations induced by the drug were investigated and compared with those caused by melphalan (L‐PAM) in SW626 human ovarian‐cancer cells. By coupling bromodeoxyuridine (BUdR) immunoreaction with biparametric flow‐cytometric (FCM) analysis, we investigated the cell‐cycle phase perturbation induced by tallimustine or L‐PAM, considering separately the cells which, during the 1‐hr treatment, were in the S phase or in G1‐G2/M phases of the cell cycle. L‐PAM delayed the S‐phase progression of cells exposed to the drug when they were in S phase, with a consequent accumulation of cells as soon as they reached the G2 phase. In contrast, the S‐phase cells treated with tallimustine were not perturbed during the DNA‐synthesis phase progression, and were blocked in G2 only after they had passed through the G1/S transition of a new cell cycle. In cells which were in G1 or G2/M phases during drug treatment, tallimustine and L‐PAM caused similar accumulation in G2. The differences in the cell‐cycle perturbation caused by tallimustine and L‐PAM may well be related to the different DNA damage the 2 drugs produced. These findings emphasize the different properties of DNA‐minor‐groove alkylating agents and conventional ones. © 1995 Wiley‐Liss, Inc.
Rodent model of systemic mammary tumor disease by surgical removal of the spontaneously metastasizing SMT2A mammary carcinoma: Inhibitory effect of the stable prostacyclin Analogue cicaprost on occult metastasis
Authors: Schirner Michael , Schneider Martin R. 
Published: February 2007

AbstractCicaprost, a stable prostacyclin Analogue, has been shown to be anti‐metastatically active in a series of metastasizing rodent tumors. Start of treatment with cicaprost immediately before tumor implantation was a characteristic feature of our previous investigations. We have reported that in rats bearing mammary‐fat‐pad‐implanted SMT2A mammary carcinoma, cicaprost treatment starting before tumor implantation led to a strong decrease in the number of lung metastases. In order to determine the effect on occult tumor metastasis, the present study examined the effect of starting treatment when tumor metastasis is already present. Cicaprost in daily oral doses of 0.1 mg/kg given from day 10 to day 32 reduced the number of lung metastases by about 75% compared with the control, whereas surgical removal of palpable primary tumors on day 5 or day 10 failed to influence lung metastasis. Using different treatment schedules, a pronounced reduction of the number of lung metastases was achieved by administration of cicaprost until the end of the experiment (from day 5 to day 35), whereas short‐term treatments (from day 5 to day 15 or to day 25) were without significant effect. In rats whose SMT2A tumors were surgically removed 10 days after tumor implantation, there was a strong decrease of lung metastases by cicaprost given from day 20 to day 36. In addition to its inhibitory potential in animals with advanced tumor disease, cicaprost showed anti‐metastatic action when used in peri‐operative treatment of animals whose primary tumors had been removed. In conclusion, the present results demonstrate that cicaprost exhibits strong anti‐metastatic activity in the SMT2A rat mammary‐carcinoma model with treatment started when occult tumor metastases are already present. Results also indicate that direct effects on tumor cells may contribute to the anti‐metastatic action of cicaprost in spontaneously metastasizing tumors. © 1995 Wiley‐Liss, Inc.
Dna methylation status of the MUC1 gene coding for a breast‐cancer‐associated protein
Authors: Zrihan‐Licht Sheila , Weiss Mordechai , Keydar Iafa , Wreschner Daniel H. 
Published: February 2007

AbstractThe MUC1 gene codes for protein products that are highly expressed in human breast‐cancer tissue and that serve as tumor markers for disease progression. The factors contributing to the disease‐specific over‐expression of the MUC1 gene are under intensive investigation and are yet to be determined. A large transcribed region of the human MUCl gene is a CpG island that consists of 60‐bp tandemly repeating units, each of which contains one Smal restriction site. The methylation status of regulatory regions, upstream to the transcriptional start site, is essential for the regulation of gene expression. We therefore evaluated whether the methylation status of the various regions of the MUC1 gene may affect its expression. Using Smal, and its isoschizomer Xmal endonucleases, we demonstrated that in peripheral‐blood leukocytes (PBL‐DNA) that do not express the MUC1 gene, the repeat array is completely methylated, whereas the same sequences are entirely non‐methylated in breast‐tumor‐tissue DNA (BT‐DNA). In contrast, sequences upstream and downstream to the repeat array showed no difference in the methylation pattern in PBL‐DNA and BT‐DNA. Hypomethylation within the repeat array was also observed in other epithelial tissues that express the MUC1 gene at much lower levels to those seen in breast‐cancer tissue. These studies demonstrate that hypomethylation of the tandem repeat array is an absolute requirement for MUC1 gene expression in epithelial tissues, although in breast‐cancer tissue additional regulatory mechanisms must pertain for its over‐expression. © 1995 Wiley‐Liss Inc.
Retinoic acid and methotrexate specifically increase PHA‐E‐lectin binding to a 67‐kDa glycoprotein in LA‐N‐1 human neuroblastoma cells
Authors: Ross Sharon A. , Jones Carol S. , De Luca Luigi M. 
Published: February 2007

AbstractRetinoic acid (RA) decreased growth and increased morphologic differentiation of human neuroblastoma LA‐N‐1 cells. These phenomena correlated with a specific enhancement of PHA‐E lectin binging to a glycoprotein of MW 67 kDa (gp67). Gp67 was found susceptible to N‐glycanase and displayed BSA binding by affinity chromatography analysis. The chemotherapeutic agent methotrexate (MTX) also reduced growth and induce differentiation of LA‐N‐1 cells. In addition, the cells responded to MTX as well as to doxorubicin by a marked increase in PHA‐E binding to gp67. We conclude that reduced growth and induction of morphological differentiation of LA‐N‐1 cells correlated with increased binding of PHA‐E to gp67. © 1995 Wiley‐Liss Inc.
Therapy of human B‐cell lymphoma bearing scid mice is more effective with anti‐CD19‐and anti‐CD38‐saporin immunotoxins used in combination than with either immunotoxin used alone
Authors: Flavell David J. , Boehm Deborah A. , Emery Loretta , Moss Armorel , Ramsay Alan , Flavell Sopsamorn U. 
Published: February 2007

AbstractThe CD 19+ CD38+ human Burkitt's lymphoma cell line Ramos grows aggressively when injected intravenously (i.v.) into severe combined immunodeficient (SCID) mice, killing 100% of animals within a 33–42 day period with widely disseminated disease. Treatment commencing 7 days after i.v. injection of Ramos cells, with 3 doses of an anti‐CD 19 immunotoxin (IT; BU12‐SAPORIN) or an anti‐CD38 IT (OKTIO‐SAPORIN) led to a significant prolongation of survival compared with shamtreated controls; the anti‐CD38 IT gave the greatest prolongation of survival, but all treated animals eventually succumbed to disease. When both ITs were used in combination at equivalent dose levels, the therapeutic outcome was significantly improved over that obtained for single IT therapy, with 20% of animals surviving disease‐free to 300 days. When anti‐CD38 IT was given in combination with anti‐CD 19 antibody there was no therapeutic improvement over anti‐CD38 IT used alone. However, when anti‐CD 19 IT was given in combination with CD38 antibody, a significant prolongation of survival ensued over that obtained with anti‐CD 19 IT alone, though this was not as significantly pronounced as that obtained when both ITs were used in combination and was only as good as the survival obtained with OKT10 antibody used alone. CD 19 and CD38 are expressed on the surface of the vast majority of B‐cell lymphoma and common acute lymphoblastic leukaemia cells, and our findings provide a sound rationale for a combination immunotoxin trial in these diseases directed against both these target molecules. © 1995 Wiley‐Liss Inc.