bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug effects on CA125 antigen expression and antibody binding to cancer cells
Authors: Nakai Toshiharu , Endo Keigo , Hosono Makoto , Saga Tsuneo , Watanabe Yuji , Sakahara Harumi , Imai Kozoh , Yachi Akira , Kivozuka Yasuhiko , Ishiwata Isamu , Konishi Junji 
Published: February 2007

AbstractCA125 is a high‐molecular weight glycoprotein expressed on most serous‐type ovarian cancer and some lung adenocar‐cinoma tissues. The effects of various drugs on the release of CA125 antigen into culture medium and on monoclonal antibody (MAb) binding to cancer cells were studied using 8 human cancer cell lines, all of which expressed CA125 on their cell surfaces. The effect of dexamethasone was seen at as low a concentration as 10–9 M dexamethasone, and the release of CA125 and the binding of radiolabelled anti‐CA125 antibody were completely inhibited after exposure to 10–7 M dexamethasone. The number of antibody binding sites markedly decreased. In contrast, sodium butyrate increased CA125 expression. These findings were clearly detected in only 3 cancer cell lines and a significant effect was not seen in the 5 other cancer cell lines. Interferon‐γ, examined in 3 cell lines, suppressed in a dose‐dependent manner in 2 CA125 expression cell lines, but enhanced it in one line. No apparent effects were seen after exposure to tissue necrosis factor or interleukin‐2. These results suggest that drugs may regulate the CA125 antigen expression in some, but not all, cancer cells and may affect the biodistribution of radiolabelled MAbs.
Plasminogen activator inhibitor 1 in human carcinoma tissues
Authors: Tanaka Nobuya , Fukao Hideharu , Ueshima Shigeru , Okada Kiyotaka , Yasutomi Masayuki , Matsuo Osamu 
Published: February 2007

AbstractThe content of PAI‐1 was measured in carcinoma tissues from the stomach and colorectum divided macroscopically into 3 portions: the central part of the carcinoma, the marginal part of the carcinoma containing some normal mucosa, and the normal mucosa. Among these tissues, the highest levels of PAI‐1 antigen were found in the central part of the carcinoma. On the other hand, no PAI‐1 antigen or activity was observed in the normal mucosae. The PAI‐1 produced in the stomach and colorectal carcinoma tissues showed a non‐lytic zone with a molecular weight of 54 kDa by reverse fibrin autography, and this 54‐kDa band reacted with anti‐PAI‐1 IgG on an immunoblotted nitrocellulose membrane by the avidinbiotin complex method. The contents of PAI‐2 in the carcinoma tissues were not significantly different from those in the normal mucosa of the stomach and colorectum. In both the stomach and colorectal carcinomas, the highest value of u‐PA/total PA (sum of u‐PA and t‐PA) was observed in the central part of the carcinoma, followed by the marginal part of the carcinoma, and was lowest in the normal mucosa. We conclude that increased levels of PAI‐1 in malignant tissue of the stomach and colorectal tract may serve to modulate extra‐cellular proteolysis by u‐PA.
DNA adducts in bronchial biopsies
Authors: Dunn Bruce P. , Vedal Sverre , San Richard H. C. , Kwan Wan‐Fung , Nelems Bill , Enarson Donald A. , Stich Hans F. 
Published: February 2007

AbstractTo investigate the feasibility of measuring DNA‐carcinogen adducts in the lungs of non‐surgical patients, endobronchial biopsies were obtained from 78 patients undergoing routine diagnostic bronchoscopy. Lung cancer was present in 37 (47%) of the patients. DNA was isolated from the tissues and analyzed by HPLC‐ or nuclease‐PI ‐enriched 32P‐postlabelling, using procedures selective for aromatic adducts. Chromatograms from all 28 current smokers showed a distinctive diagonal adduct zone which was present in only 24 of 40 ex‐smokers and 4 of 10 lifetime non‐smokers. Adduct levels and chromatographic patterns were similar in bronchial tissue from different lobes of the lung, in bronchial and alveolar tissue, and in tumor and non‐tumor bronchial tissue taken from the same subject. Bronchial DNA adduct levels were strongly associated with cigarette smoking status and dropped rapidly after smoking ceased. Higher levels of DNA adducts seen in the lung‐cancer patients were mainly due to cigarette smoking. Frequent alcohol intake was the only dietary factor associated with higher levels of bronchial DNA adducts. We conclude that the level of bronchial DNA adducts is strongly associated with cigarette‐smoking history and with alcohol intake, but is not associated with lung cancer independently from its relation to smoking. The results indicate the feasibility of using 32P‐postlabelling to detect and quantitate genetic damage in bronchial biopsy specimens.
Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens
Authors: Favrot Marie C. , Combaret Valérie , Goillot Evelyne , Tabone Eric , Bouffet Eric , Dolbeau Dominique , Bouvier Rolande , Coze Carole , Michon Jean , Philip Thierry 
Published: February 2007

AbstractLFA‐3, ICAM‐1, HLA.ABC and HLA.DR expression was analyzed on 66 neuroblastoma specimens. HLA.ABC was expressed on 26 specimens, HLA.DR on 2, LFA‐3 on 20 and ICAM‐1 on 10. HLA.ABC and LFA‐3 were positive on ganglioneuroblastoma or ganglioneuroma, but they were negative on neuroblastoma, independently of the clinical staging; HLA.ABC and LFA‐3 were induced in vivo by chemotherapy in parallel with tumoral cell differentiation, in both the primary and the metastases. The expression of ICAM‐1 was restricted to 5 of the 10 low‐grade stage‐1 or stage‐2 specimens, 1 stage‐3 specimen, and the primary tumors of 2 patients with stage‐4 disease, analyzed hence at diagnosis and after chemotherapy (4 specimens); metastatic cells obtained in 1 of these patients were negative. HLA.ABC and LFA‐3 expressed on both myc N‐negative and ‐positive specimens, whereas ICAM‐1 was restricted to MYCN‐negative specimens. LFA‐3 diffusely stained partially differentiated neuroblasts, Schwann cells and ganglion cells. The expression of HLA.ABC on differentiated neuroblasts varied from one sample to another and within the same tumor; Schwann cells were strongly positive, but ganglion cells were negative. In positive samples, ICAM‐1 was expressed on differentiated neuroblasts and Schwann cells, but negative on ganglion cells; however, most of the differentiated tumors were ICAM‐1‐negative, suggesting ICAM‐1 induction by unknown local signal. The 4 markers were negative on undifferentiated neuroblasts. The distribution of these 4 markers on clinical specimens was in agreement with their reactivity on fetal tissues, as well as with results obtained on neuroblastoma cell lines before and after in vitro treatment with IFN‐γ.
Laminin receptors, collagenase IV and prognosis in node‐negative breast cancers
Authors: Daidone Maria Grazia , Silvestrini Rosella , D'Errico Antonia , Fronzo Giovanni Di , Benini Elvira , Mancini Antonio M. , Garbisa Spiridione , Liotta Lance A. , Grigioni Walter F. 
Published: February 2007

AbstractIn 187 node‐negative breast cancers, the expression of laminin receptors and collagenase IV was directly related in 52% of cases, independently of pathological (tumor size and histology) and biological (estrogen receptors and proliferative activity) features. Moreover, the presence of laminin receptors and collagenase IV did not appear to influence tumor proliferative activity, evaluated as 3H‐thymidine labelling index. In this case series, relapse‐free survival and overall survival at 6 years were significantly affected by tumor size, hormone receptor status and proliferative activity. Conversely, high levels of laminin receptors and collagenase IV failed to influence relapse‐free or overall survival, whereas they were strong indicators of local‐regional diffusion of the disease.
Estrogen and progesterone receptors in cervical human papillomavirus related lesions
Authors: Monsonego Joseph , Magdelenat Henri , Catalan François , Coscas Yves , Zerat Laurent , Sastre Xavier 
Published: February 2007

AbstractAccording to recent studies showing that human papilloma‐ virus (HPV) infections can be influenced by sex steroid hormones, we performed estrogen (ER) and progesterone (PgR) receptor assays in fresh frozen biopsies of genital‐HPV‐related lesions. Seventy‐three women with normal cervix, condyloma, low‐ and high‐grade CIN and squamous carcinoma were evaluated in comparison with 15 persons with vulvar and 9 with penile papillomavirus‐assoclated lesions. HPV genotypes were determined by dot‐blot hybridization. Non‐cervical lesions did not express HR. Condyloma on squamous metaplasia of the cervix and high‐grade CIN expressed high levels of HR, particularly PgR (mean 4,086 and 4,518 fmoles/g tissue, respectively). Cervical squamous carcinoma expressed very low concentrations of PgR in a limited number of cases. High levels of PgR were correlated with high‐grade CIN(p <0.05),HPV16–18‐associated lesions (p <0.01) and ER were correlated to HPV6–11‐related lesions (p < 0.01). The levels were independent of age, cycle stage and oral contraception. Morphological localization of PgR, using an immunocytochemical method using a monoclonal antibody (MAb) (PR‐ICA), showed intense homogeneous staining in the nuclei of the stromal fibroblasts underlying dysplastic epithelium and condyloma on squamous metaplasia. These results suggest that, under in vivo conditions, sex steroid hormones, particularly progesterone, may act indirectly on HPV‐infected epithelial cells and be implicated as co‐factors in HPV‐related cervical neoplasia. They could explain the relative predisposition to malignant transformation of the cervix as compared with vulvar and penile mucosa.
Expression of collagenase‐related metalloproteinase genes in human lung or head and neck tumours
Authors: Muller D. , Breathnach R. , Engelmann A. , Millon R. , Bronner G. , Flesch H. , Dumont P. , Eber M. , Abecassis J. 
Published: February 2007

AbstractWe address the question as to whether increased metalloproteinase production might be related to the high regional recurrence rate of some carcinomas, and particularly head and neck squamous‐cell carcinomas (SCC). Northern blot of total RNA prepared from 26 lung carcinomas, 107 head and neck carcinoma samples and corresponding normal tissue samples demonstrates the frequent and sometimes concomitant over‐expression of the 2 stromelysin genes, the type‐1 collagenase gene and the pump‐1 gene in the head and neck tumour tissue samples. In these SCC, over‐expression of the 2 stromelysin genes and the type‐1 collagenase gene (but not the pump‐1 gene) is associated with a high degree of tumour differentiation. Moreover, a tumour with high levels of the stromelysin mRNAs is more likely to show high local invasiveness, suggesting that the stromelysins may be implicated in the clinical course of head and neck tumours. Evaluation of the corresponding mRNA levels may prove a useful indicator for predicting the clinical aggressiveness of these tumours.
Altered expression of P‐glycoprotein and cellular adhesion molecules on human multi‐drug‐resistant tumor cells does not affect their susceptibility to NK‐ and LAK‐mediated cytotoxicity
Authors: Scheper Rik J. , Dalton William S. , Grogan Thomas M. , Schlosser Arno , Bellamy William T. , Taylor Charles W. , Scuderi Phil , Spier Catherine 
Published: February 2007

AbstractDrug resistance has been associated with resistance to NK‐ and LAK‐cell‐mediated cytotoxicity. We evaluated this issue in human cell lines, using multiple myeloma cells (8226) and 2 multi‐drug‐resistant (MDR) sublines selected using doxorubicin (8226/Dox40) and mitoxantrone (8226/MR40). In parallel, we studied the human breast carcinoma cell line series MCF7, MCF7/D40 and MCF7/Mitox. Unlike the sensitive parental cell lines, all 4 sublines display MDR‐patterns of resistance, with the P‐glycoprotein pump (P‐170) detected only in the doxorubicin‐selected sublines. Flow cytometric and immunocytochemical analyses showed expression of cellular adhesion molecules ICAM‐1 and LFA‐3, and MHC‐Class‐1 (MCF7/D40 only), to be decreased in the doxorubicin‐selected MDR‐sublines, whereas expression of CD56 (Leu 19) was strongly up‐regulated in 8226/Dox40. Lysis of P‐170‐positive MDR tumor cells by NK or LAK cells was, however, unaffected by these alterations, suggesting redundancy in effector: target‐cell adhesion pathways. Mitoxantrone‐selected tumor cells did not display P‐170, nor did they show altered expression of cellular adhesion molecules. Their susceptibility to NK or LAK cytolysis was also unimpaired as compared to the parental cell lines. Clinically, these results imply that immunotherapeutic modalities aiming at increased natural killer functions deserve full consideration even in patients who have become refractory to further cytostatic drug treatment.
Vascular anatomy and organ‐specific tumor growth as critical factors in the development of metastases and their distribution among organs
Authors: Arguello Francisco , Baggs Raymond B. , Eskenazi Allen E. , Duerst Reggie E. , Frantz Christopher N. 
Published: February 2007

AbstractWe have examined with 19 tumor cell lines the discrete roles that vascular anatomy and tumor‐cell‐organ‐affinity play in the development of metastases and their distribution among organs. Spontaneous metastases of B16‐G3.26 melanoma cells from a primary tumor growing in the foot pad of mice, or experimental metastases 21 days after intravenous tumor‐cell injection resulted in tumor colonies only in the lungs. In contrast, when the lung microvasculature was bypassed, and the same cells given by systemic intra‐arterial (s.i.a.) injection, large tumor colonies developed selectively in the ovaries, adrenal glands and bones, but rarely in the lungs. When animals injected i.v. were allowed to live with lung metastases for a long period of time, small tumor colonies began to develop in extra‐pulmonary organs with a distribution identical to that seen after s.i.a. injection. Seven murine tumor cell lines (previously characterized by their ability to colonize primarily the lungs after i.v. injection) and 7 of the 8 studied human tumor cell lines colonized different specific extra‐pulmonary organs after s.i.a. injection, frequently producing metastatic syndromes commonly described in patients with cancer, but rarely seen in animal models of metastasis. These results suggest that metastatic cells, even those capable of colonizing specific organs, do not freely circulate in the blood stream and lodge in specific tissues. In contrast, the cells must establish a vascular route of access to the target organ, e.g., through the systemic circulation from metastatic tumors in the lungs. Two cell lines considered to be tumorigenic but non‐metastatic failed to colonize the lungs or extra‐pulmonary organs after i.v. injection, but readily colonized specific organs after s.i.a. injection. Thus, tumor cells considered to be non‐metastatic may be indeed metastatic if they are provided with vascular access to an organ more congenial to their growth requirements.
In vitro and in vivo modulation of multi‐drug resistance with amiodarone
Authors: Van Der Graaf W. T. A. , De Vries E. G. E. , Uges D. R. A. , Nanninga A. G. , Meijer C. , Vellenga E. , Mulder P. O. M. , Mulder N. H. 
Published: February 2007

AbstractThe modulating effect on drug resistance of amlodarone (AM) and its metabolite desethylamiodarone (DEA) was studied in a P‐glycoprotein‐positive human colon carcinoma cell line COLO 320, and a human small‐cell lung carcinoma cell line GLC4 and its adriamycin (Adr)‐resistant subline GLC4‐Adr (both P‐glycoprotein‐negative). AM, DEA and verapamil induced an increase in cytotoxicity of Adr, vincristine and etoposide (VP16) In COLO 320 cells, while in the GLC4 and GLC4‐Adr cell line no effect was seen. In the COLO 320 cell line, AM caused more intracellular, and especially intranuclear, fluorescence of Adr and more Adr‐induced DNA strand breaks as compared to Adr alone. Moreover, an increase in VP16‐induced topoisomerase II‐DNA complexes was observed when AM was added. Competition between AM and Adr for the same efflux pump was suggested In efflux studies. The colony‐forming unit granulocyte macrophage (CFU‐GM) assay showed no increase In cytotoxicity of Adr when AM was added. Fourteen patients with Adr‐resistant tumors were treated with Adr and AM. In these patients, peak serum levels of AM plus DEA of 10 μ.M were reached. Patient serum (20%) obtained after the first i.v. AM infusion induced in vitro significantly more cell kill of Adr in COLO 320 cells. Apart from a transient first‐degree AV block In one patient, no cardiac toxiclty was observed with the combination of Adr and AM. Bone‐marrow toxicity was the same as expected from Adr alone in these patients. One of the 13 evaluable patients obtained a partial remission.
Etoposide with lonidamine or pentoxifylline as modulators of alkylating agent activity in vivo
Authors: Tanaka Juichi , Teicher Beverly A. , Herman Terence S. , Holden Sylvia A. , Dezube Bruce , Frei Emil 
Published: February 2007

AbstractIn an effort to improve the additive anti‐tumor efficacy of commonly used alkylating agents, the topoisomerase‐II inhibitor etoposide was used in combination with either the mitochondrial poison and energy‐depleting agent lonidamine or the hemorheologic agent and tumor‐blood‐flow‐increasing agent pentoxifylline. In the FSallC murine fibrosarcoma system, these modulators were evaluated for modulation of whole‐tumor cell killing vs. bone‐marrow CFU‐GM toxicity with the alkylating drugs CDDP, CTX, L‐PAM or BCNU. Etoposide alone was essentially additive with the alkylating drugs for both tumor‐cell and bone‐marrow killing, except for BCNU, where a substantial increase in tumor‐cell killing occurred (0.5 to 2.0 logs over the dose range of BCNU tested) without a significant increase in bone‐marrow toxicity. Etoposide plus lonidamine was significantly more active than etoposide alone only with CTX and BCNU in tumor‐cell vs. bone‐marrow killing. Etoposide plus pentoxifylline was also most active with these two alkylating agents, where increases in tumor‐cell killing of 0.5 to 1.0 log were observed. Hoechst‐33342‐defined tumor‐cell sub‐population studies revealed that etoposide significantly improved the killing of dim (putative hypoxic) cells by CDDP, but neither lonidamine nor pentoxifylline significantly improved killing of bright or dim cells together. With CTX, etoposide plus lonidamine or pentoxifylline substantially improved killing of dim cells over etoposide alone (each by about 0.8 logs). These data indicate that a therapeutic advantage may be achievable by combining etoposide with lonidamine or pentoxifylline for use with alkylating drugs.
c‐erbB‐2 proto‐oncogene expression and its relationship to survival in gastric carcinoma: An immunohistochemical study on archival material
Authors: Jain S. , Filipe M. Isabel , Gullick W. J. , Lineman Jacqueline , Morris R. W. 
Published: February 2007

AbstractThe c‐erbB‐2 proto‐oncogene encodes a growth factor receptor which is over‐expressed in a variety of human adenocarcinomas. Recent reports suggest that it may be of value in arriving at prognosis in breast and ovarian cancer. In this study, c‐erbB‐2 expression was investigated in 93 routinely processed cases of gastric carcinoma, using an immunohisto‐chemical technique. c‐erbB‐2 membrane immunoreactivity was observed in 11% (10/93) of tumours, all of whkh were of the well differentiated intestinal type (p< 0.01). Overall, patients with tumours expressing this proto‐oncogene had a significantly improved prognosis (p< 0.05). Within the group of intestinal‐type tumours, those that were c‐erbB‐2‐positive formed a distinct sub‐population which had a better prognosis (p< 0.02), suggesting possible differences in aetiology.
Trisomy 12 and K‐ras‐2 Amplification in human ovarian tumors
Authors: Yang‐Feng Teresa L. , Li Shi‐Bo , Leung Wah‐Ying , Carcangiu Maria L. , Schwartz Peter E. 
Published: February 2007

AbstractCytogenetic analysis was performed on 11 benign and borderline ovarian tumors. Trisomy 12, identified as a sole abnormality in 6 tumors, is likely a specific karyotypic change in different benign and borderline tumors and may well be a primary chromosomal lesion in these tumors. The possible association between amplification of the proto‐oncogene K‐ras‐2 which Is located on chromosome 12 and trisomy 12 was Investigated. DNA blotting analysis of 64 tumors indicates that trisomy 12 does not seem to be related to K‐ras‐2 amplification in ovarian tumors. K‐ras‐2 amplification was observed in 3 high‐grade tumors from 3 patients with metastases.
Tumoricidal activity and cytokine secretion by tumor‐infiltrating macrophages
Authors: Brunda Michael J. , Sulich Viveca , Wright Rosemary B. , Palleroni Alicia V. 
Published: February 2007

AbstractMurine macrophages from different anatomical sites were compared for their ability to become tumoricidal and to secrete interleukin‐l (IL‐I) and tumor necrosis factor (TNF) following stimulation in vitro by several biological response modifiers (BRM). Peritoneal macrophages (PM), alveolar macrophages (AM), and tumor‐infiltrating‐macrophages (TIM), isolated from B16F10 melanoma colonies in the lung, were incubated overnight with BRM [recombinant murine in‐terferon gamma (rMulFN‐γ), lipopolysaccharide (LPS), muramyl dipeptide (MDP)], either alone or in combination. PM exhibited an increased cytotoxic response following incubation with LPS or rMulFN‐γ but not with MDP. Both AM and TIM were induced to become tumoricidal following incubation with rMulFN‐γ plus LPS or rMulFN‐γ plus MDP but not after stimulation with any BRM alone; the level of cytotoxicity obtained with TIM incubated with rMulFN‐γ plus LPS was slightly lower than that observed with PM or AM, while with rMulFN‐γ plus MDP both AM and TIM had lower cytotoxicity than PM. Secretion of IL‐I and TNF was observed in PM stimulated with LPS or MDP but not with rMulFN‐γ. Likewise, secretion of IL‐I by AM or TIM was also induced with LPS, although Jess than that obtained with PM. AM stimulated with LPS secreted larger amounts of TNF than PM while TIM secreted very low amounts of TNF. However, this result may be a consequence of the enzymatic isolation procedure used to obtain TIM since TNF secretion was also impaired in LPS‐stimulated normal lung macrophages isolated by a similar enzymatic procedure, or enzyme‐treated PM. Our results suggest that TIM obtained from lung metastases share certain functional characteristics with normal AM and respond to BRM in like manner with respect to induction of tumoricidal activity and cytokine secretion.
A secreted Mr ∼ 40,000 glycoprotein specifically induced by glucocorticoids in a rat colon carcinoma cell line
Authors: Denis Marc G. , Chadeneau Corinne , Pleignet Corinne , Lustenberger Patrick 
Published: February 2007

AbstractGlucocorticoid hormones are thought to play a role in car‐cinogenesis, as they regulate cell differentiation and proliferation. We have previously shown that dexamethasone inhibits the growth of a rat colon carcinoma cell line, and induces the secretion of an Mr ∼ 40,000 protein. We now report that the synthesis and the release in the culture medium of this protein is stimulated specifically by glucocorticoid agonists, and not by other steroid hormones. The anti‐glucocorticoid RU 38486 is inefficient and suppresses the induction of this protein by dexamethasone. Induction is sensitive to actinomycin D, suggesting that regulation may be exerted by altering the rate of mRNA synthesis. Characterization of culture medium from dexamethasone‐treated cells revealed that the Mr ∼ 40,000 protein is glycosylated, and can be further separated from other secreted proteins by high‐performance anion‐exchange chromatography.