bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estradiol and EGF requirements for cell‐cycle progression of normal human mammary epithelial cells in culture
Authors: Colomb Evelyne , Berthon Philippe , Dussert Christophe , Calvo Fabien , Martin Pierre‐Marie 
Published: February 2007

AbstractThe purpose of our study was to show the feasibility of accurately investigating the factors likely to control cell proliferation of normal human mammary epithelial (HME) cells, using a scanning cytometric method. The methodology was previously developed with the SAMBA 200 cell image processor to characterize in situ the cell‐cycle phases of HME cells. Since various compartments constitute the mammary epithelium, cells obtained after reduction mammoplasty were cultured in a medium with a low calcium content (0.06 mM) to provide proliferating normal HME cells while maintaining their differentiation characteristics. Estradiol and EGF requirements for cell‐cycle phase progression of these cells were examined. Then, we showed that 2 normal HME cell cultures displaying different phenotypic characteristics may differently progress through the cell cycle under the same hormonally defined conditions. Cell‐cycle progression of the epithelial cells presenting luminal phenotype was induced only by sequential stimulation/pre‐treatment with estradiol followed by EGF treatment; this progression was enhanced when estradiol was maintained during EGF treatment. This definite order demonstrated that estradiol could have a permissive effect on EGF mitogenic activity. In contrast, epithelial cells likely to be localized in the basal position in the mammary gland showed the same proliferating activity whatever the estradiol and EGF treatment. These cells progressed profusely in cell cycle, independent of exogenous estradiol and EGF contribution, but they remained sensitive to estradiol regarding EGF‐receptor detection. Our results suggest autonomous proliferation of these cells through an autocrine pathway, in the absence of negative regulators.
Dipeptidyl peptidase iv expression identifies a functional sub‐population of breast fibroblasts
Authors: Atherton Amanda J. , Monaghan Paul , Warburton Michael J. , Robertson David , Kenny A. John , Gusterson Barry A. 
Published: February 2007

AbstractThe immunocytochemical distribution of the cell‐surface enzyme dipeptidyl peptidase IV (DPP IV) has been studied in the human breast at the light and ultrastructural level. The presence of the enzyme was demonstrated on the cell membranes of interlobular fibroblasts, whilst intralobular fibroblasts were DPP‐IV‐negative. A fluorograph, after immunoprecipitation of 35S‐methionine‐labelled proteins of fibroblasts from primary breast cultures with an anti‐serum to DPP IV, demonstrated a band at 135 kDa consistent with the presence of the enzyme. The clear delineation of 2 functionally distinct sub‐populations of breast fibroblasts was maintained in benign fibro‐adenomas and cystosarcoma phyllodes, both tumour types having growth characteristics of intralobular stroma. This observation has important implications for both normal breast biology and for breast carcinogenesis.
Oesophageal mucosa in a population at risk of oesophageal cancer: Post‐mortem studies
Authors: Jaskiewicz Kaz , Banach Lech , Mafungo Victor , Knobel Gideon J. 
Published: February 2007

AbstractWe performed post‐mortem studies of oesophageal mucosa from 513 consecutive autopsies of cases who died from unnatural causes or from diseases not related to the oesophagus. Of these, 170 cases were rural blacks from endemic high‐risk areas, 98 were urban blacks at high risk, 158 were coloureds at moderate risk and 87 whites at low risk for oesophageal carcinoma. Oesophagi were studied macroscopically and histologically to determine malignant and precursor lesions. A prevalence of 1.0 to 1.8% of squamous carcinoma and 7 to 7.5% of mucosal dysplasia was detected in cases older than 30 years from high‐risk urban and rural population groups. These results are in accord with our previous cytological and endoscopical screening studies. No significant differences in the prevalence of oesophagitis, glycogenic acanthosis and atrophy were found in the groups studied. A study of oesophageal melanocytes showed a 3% prevalence, unrelated to dysplastic and malignant lesions, and suggested that these cells were of little if any practical significance as precursor lesions.
Intramural metastasis of thoracic esophageal carcinoma
Authors: Kato Hoichi , Tachimori Yuji , Watanabe Hiroshi , Itabashi Masayuki , Hirota Teruyuki , Yamaguchi Hajime , Ishikawa Tsutomu 
Published: February 2007

AbstractOf 393 patients with squamous‐cell carcinoma in the thoracic esophagus, 60 were found by histologic examination to have intramural metastasis. Metastases in 50 of these were identified by gross inspection. There appeared to be no preference for location proximal to the primary lesion. Eighteen patients had metastasis to the gastric wall, which suggested the existence of communicating lymphatic channels between the wall of the esophagus and the stomach. All 60 primary tumors invaded beyond the submucosa. These 60 patients (group A) were compared with a group of matched control patients without intramural metastasis (group B). The tumor size in group A was significantly larger than in group B (p< 0.01). The number of patients with lymph‐node metastasis was significantly higher in group A (p< 0.01), and the average number of positive nodes in group A was greater than in group B (p< 0.01). Recurrent disease in the mediastinal lymph nodes and in the liver is characteristic of group A. The survival curve for patients in group A was significantly lower than that for group B (p< 0.001). Conventional radiotherapy or chemotherapy after surgery were ineffective in improving prognosis. These results indicate that the presence of intramural metastasis is an important factor to consider when evaluating the prognosis of patients with squamous‐cell carcinoma of the esophagus.
Effects of interferons on the expression of the proto‐oncogene her‐2 in human ovarian carcinoma cells
Authors: Marth Christian , Cronauer Marcus V. , Doppler Wolfgang , Öfner Dietmar , Ullrich Axel , Daxenbichler Günter 
Published: February 2007

AbstractThe over‐expression of the proto‐oncogene HER‐2 (c‐erb B‐2/ neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon‐gamma (IFN‐γ)‐mediated reduction in HER‐2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN‐γ‐sensitive human breast cancer cell lines. We extended our observations also to IFN type I, α and ω. The expression of the oncogene was measured by both the p185HER‐2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER‐2 in the ovarian carcinoma cell lines OVCAR‐3, HTB‐77, 2774 and SKOV‐6, and in the SKUT‐2 endometrial carcinoma cells. In contrast, SKOV‐8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN‐γ reduced proto‐oncogene expression. In the SKBR‐3 human mammary carcinoma cells, neither IFN type had an effect on HER‐2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER‐2 protein specifically inhibited anchorage‐independent growth of SKBR‐3 and HTB‐77 cells. Expression of the oncogene HER‐2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.
Blood coagulation changes in nude mice bearing human colon carcinomas
Authors: Bani M. R. , Falanga A. , Alessio M. G. , Radice E. , Consonni R. , Giavzzi R. , Donati M. B. 
Published: February 2007

AbstractWe studied several blood coagulation parameters and tumor tissue procoagulant activity (PCA) in nude mice bearing human colorectal carcinomas (HCC). In a control group of 51 tumor‐free nude mice, platelet number was 1.2 ± 0.03 ± 106/μl, thrombotest activity 90% ± 2.6 and fibrinogen 172 ± 11 mg/dl. The same parameters were studied in nude mice (n = 71) bearing 7 different HCC lines subcutaneously (s.c.). The results did not significantly differ from those in control mice but there was broad variability among groups of mice injected with different HCC lines, ranging from 0.36 to 2.55 ± 106/μl for platelets, from 100 to 28% for thrombotest activity and from 42 to 460 mg/dl for fibrinogen. The results were significantly (p < 0.05) different from those in the tumor‐free group when each group of HCC‐bearing animals was analyzed individually. A malignant HCC line that grew in the liver of nude mice (n = 24) significantly (p < 0.001) reduced thrombotest activity (58% ± 5.9). The PCA of tissue extracts from tumors grown s.c. in nude mice was assayed. All the HCC xenografts expressed PCA which differed significantly for the various tumor lines (from 25.5 ± 1.9 to 2.8 ± 0.6 unit/mg in tumor tissue). Cancer procoagulant (CP), a cysteine proteinase with a direct factor‐X‐ activating effect, was present in different amounts (84.7 ± 4.3 to 59.5 ± 9.0%) in the tumors. Our results indicates that the nude mouse is a suitable model for evaluating the hemostatic changes induced by human tumors and may represent a tool for investigating the underlying biochemical mechanisms.
Insulin dependence of murine lymphoid T‐cell leukemia
Authors: Pillemer Graciela , Lugasi‐Evgi Hefziba , Scharovsky Graciela , Naor David 
Published: February 2007

AbstractThe in vitro proliferation of the spontaneous lymphoid T‐cell leukemia designated LB was enhanced by physiological, intermediate and supraphysiological concentrations of insulin. The enhancing effect was observed in both serum‐free medium (SFM) and medium containing low concentrations of serum. Guinea‐pig anti‐insulin serum, but not guinea‐pig normal serum, inhibited the proliferation of LB cells incubated either in medium containing serum alone or in medium containing serum and supplemented with insulin. This finding suggests that LB cells use serum insulin as a growth factor. Insulin‐like growth factors I (IGF‐I) and II (IGF‐II) failed to stimulate an appreciable proliferation in LB cells, whereas in the same experiment insulin markedly enhanced the proliferation of this lymphoid leukemia. Furthermore, the concentration of unlabelled insulin required to displace 50% of 125I‐insulin bound to LB cells was 3 orders of magnitude lower than the concentration of IGF‐I required to achieve the same displacement. Our findings indicate that interaction of insulin with its own receptor, and not with IGF‐I receptor, triggers the proliferation of LB cells. Radio‐receptor assays revealed that LB cells express approximately 3,200 molecules of high affinity (Kd = 10−9 M) insulin receptor per cell. None of 7 other tumor cell lines tested responded to insulin. The proliferation of insulin‐stimulated LB cells was also inhibited with tyrphostin, a tyrosine kinase blocker analogous to tyrosine, which perhaps blocks the tyrosine kinase activity of the insulin receptor β‐chain.
Tumor‐antigen‐specific humoral immune response of animals to anti‐idiotypic antibodies and comparative serological analysis of patients with small‐cell lung carcinoma
Authors: Lehmann Hans‐Peter , Zwicky Caroline , Waibel Robert , Stahel Rolf A. 
Published: February 2007

AbstractWe have previously developed 3 monoclonal anti‐idiotypic antibodies (Ab2) of LOU rat origin directed against the binding site of the murine monoclonal IgM LAM8, which recognizes the small‐cell lung carcinoma (SCLC)‐associated sialoglycoprotein antigen sGP90–135. The aim of this study was to compare the efficiencies of these 3 Ab2, designated LY8–229, LX8–531 and LX8–632, to induce antigen‐specific immunity in different animal species without prior exposure of the recipients to the nominal antigen, and thereby possibly select an Ab2 candidate for active immunotherapy against SCLC in patients. The feasibility of this approach was further evaluated by a serological analysis of patients with SCLC compared with healthy individuals, in whom the spontaneous antibody reactivities against SCLC cell lines and Ab2 were tested. LY8–229 was shown to be the most effective Ab2 in inducing antigen‐specific antibodies in BALB/c mice, CBA/J/Zur mice and one NZW rabbit. Furthermore, LY8–229 was the only Ab2 against which significantly elevated idiotype‐specific antibody reactivities existed in sera of patients with SCLC. These reactivities correlated positively with binding to antigen‐positive tumor cells. Our findings suggest that LY8–229 represents in its reactivity pattern the nominal SCLC antigen in humans also, and therefore may be of diagnostic and possibly therapeutic relevance for patients with SCLC.
Tissue vitamin a repletion is impaired by exposure to carcinogen
Authors: Edes Thomas E. , Kwan Sandra M. , Buckley Christopher S. , Thornton William H. 
Published: February 2007

AbstractVitamin A appears to exert a protective effect against certain cancers. Epithelial cancers, such as those of the skin, bladder, oropharynx and respiratory tract, have the strongest association with vitamin A. These same cancers are causally associated with exposure to carcinogens such as benzo(α)pyrene (BP), a product of combustion found in cigarette smoke and charbroiled meat. This study was designed to determine whether BP exposure affects tissue vitamin A nutriture. Female Sprague‐Dawley rats were randomized to purified diets, sufficient or deficient in vitamin A, and with or without 200 mg BP/kg feed. Rats were killed after 4 or 6 weeks. Serum, liver and lungs were assessed for vitamin A levels; trachea, stomach, small intestine and bladder were examined for histologic change. Lack of dietary vitamin A resulted in a profound decrease in vitamin A in the serum, liver and lungs (p < .005). No histologic changes were evident in any tissues examined. Serum vitamin A was not affected by dietary BP. In vitamin‐A‐sufficient rats, dietary BP caused a significant decline in hepatic and lung vitamin A. In rats fed vitamin‐A‐deficient diets, dietary BP had no effect on tissue vitamin A. We conclude that chronic exposure to the carcinogen BP leads to tissue depletion of vitamin A, despite a vitamin‐A‐sufficient diet. We postulate that BP impairs tissue repletion by metabolizing incoming vitamin A rather than in situ vitamin A, since BP had no effect on tissue vitamin A levels in rats fed a diet devoid of vitamin A. This BP‐induced vitamin depletion may eventually have a deleterious effect on epithelial tissue health, and may help to explain the association between vitamin A and cigarette‐smoke‐related cancers.
Enhanced induction of colon carcinogenesis by azoxymethane in wistar rats fed a low‐protein diet
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Taniguchi Haruo 
Published: February 2007

AbstractThe effects of ad libitum feeding of synthetic, low‐protein diets on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), on the norepinephrine concentration in the colon wall tissue and on the labelling index of colon mucosa were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of AOM and were given synthetic diets of equal calory content containing 25% casein (normal‐protein diet), 10% casein (low‐protein diet) or 5% casein (very‐low‐protein diet). Administration of the low‐ and very‐low‐protein diets resulted in significant increases in the incidence and number of colon tumors at week 30. However, it did not affect the histology of the colon tumors. The low‐ and very‐low‐protein diets also resulted in significant increases in norepinephrine concentration in the proximal and distal portions of the colon wall and in the labelling indices of both parts of the colon mucosa. Our findings indicate that low‐ and very‐low‐protein diets enhance colon carcinogenesis and that this may be related to their effects in increasing the norepinephrine level in the colon wall and in stimulating proliferation of colon epithelial cells.
Comparative biological responses of rabbits infected with human T‐lymphotropic virus type I isolates from patients with lymphoproliferative and neurodegenerative disease
Authors: Lairmore Michael D. , Roberts Beverly , Frank David , Rovnak Joel , Weiser M. Glade , Cockerell Gary L. 
Published: February 2007

AbstractAn experimental rabbit model was used to determine host responses to infection by various human T‐lymphotropic virus type‐I (HTLV‐I) strains. Seven groups of 4 to 5 rabbits each were inoculated with lethally‐irradiated HTLV‐I‐infected cell lines derived from patients with adult T‐cell leukemia/lymphoma or from patients with HTLV‐I‐associated myelopathy. Four separate control groups of 2 rabbits each were inoculated with similarly prepared HTLV‐I‐negative cells derived from rabbits or humans. Anti‐viral antibody responses were assessed by immunoblot assay and hematologic parameters were measured using automated cell counters and cytologic staining. The virologic status of challenged rabbits was determined by co‐culture and HTLV‐I antigen capture assay, as well as by polymerase chain reaction (PCR) amplification of HTLV‐I DNA from peripheral blood mononuclear cells (PBMC) or tissues. The HTLV‐I inocula could be separated into groups based upon their infectivity to rabbits: highly infectious strains elicited intense serologic responses and were detected frequently in tissues by antigen and PCR assays, while other strains were moderately to poorly infectious, induced weak antibody responses and were infrequently detected by antigen and PCR assays. Overall, PBMC appeared to have the greatest quantity of HTLV‐I containing cells, while bone marrow was a poor source of virus. No clinical or hematologic abnormalities were evident during the 24‐week course of infection. Taken together, our results suggest there is heterogeneity in the biological response to HTLV‐I infection which is, in part, dependent on the infecting strain of virus.
Elevated activities of protein kinase C and tyrosine kinase correlate to leukemic cell aggressiveness
Authors: Aflalo Esther , Wolfson Marina , Ofir Rivka , Weinstein Yacob 
Published: February 2007

AbstractWe report a linkage between cell aggressiveness, protein kinase C (PKC) activity, tyrosine kinase (PTK) activity and serum requirement. We used 2 leukemic cell lines induced by Moloney murine leukemia virus (MLV). One line was highly aggressive (BS‐24‐1) and required low serum concentrations (3%) for optimal growth in comparison to the less aggressive line (RO2T) that needed 10% serum for optimal growth. The more malignant cells exhibited higher PKC and PTK activity. This activity was independent of serum concentration between 0.01–10%. In contrast, the weakly malignant cells need a high serum concentration (10%) for optimal PKC or PTK activity. Immunoblot analysis revealed a higher level of PKC protein in the BS‐24‐1 cells than in the RO2T cells. Serum induction of PKC activity did not change the amount of PKC protein in the cytosol or the membrane fractions, indicating post‐translational mechanism regulation of PKC. We suggest that the aggressiveness of BS‐24‐1 resulted from its ability to become independent of growth regulation by serum factors, via autocrine stimulation of PKC and PTK.
Immunization against polyoma tumors with synthetic peptides derived from the sequences of middle‐and large‐T antigens
Authors: Reinholdsson‐Ljunggren Git , Ramqvist Torbjörn , Ährlund‐Richter Lars , Dalianis Tina 
Published: February 2007

AbstractWe have used 9 synthetic peptides corresponding to sequences of polyoma virus small‐T, middle‐T and large‐T antigens as immunogens in order to map antigenic epitopes that can induce polyoma‐tumor‐specific immunity in different mouse strains. We found that immunization of mice with synthetic peptides derived from amino acid (aa) sequences common to all 3 T‐antigens (aa 1–19), or sequences common to only middle‐T and small‐T (aa 162–176), as well as synthetic peptides unique for middle‐T (aa 269–282 and 371–381), or unique for large‐T (aa 108–124, 316–333 and 436–449) can induce immunity against polyoma tumors. The synthetic peptides can be divided into 3 types with regard to immunogenicity; (i) peptides that immunize in more than one mouse strain and may represent immunodominant sites, (ii) peptides that may be immunogenic in only one strain, and thus strain‐specific, and finally (iii) peptides that do not immunize in the strains tested so far.
Tumor‐cell dissociation at the invasion front: A new prognostic parameter in gastric cancer patients
Authors: Gabbert H. E. , Meier S. , Gerharz C. D. , Hommel G. 
Published: February 2007

AbstractTumor‐cell dissociation (TCD) is a well‐known feature at the invasion front of malignant tumors, but little attention has so far been paid to its biological significance. Therefore, the aim of the present study was to score the degree of TCD at the invasion front (TCD 0–3) in a retrospective series of 445 gastric cancer patients and to compare its prognostic significance with the parameters T‐stage, tumor size, grade of tumor differentiation, lymph‐node involvement and vascular invasion. We could show that highly significant differences (p < 0.0001, log‐rank test) existed between the 5‐year survival rates of patients with different degrees of TCD (TCD 0:92.3%; TCD 1:62.1 %; TCD 2: 41.2%. TCD 3:38.5%) and that these differences were independent of T‐stage 2, tumor size and grade of tumor differentiation. Univariate Cox regression analysis showed that in intestinaltype carcinomas, T‐stage (Chi‐square: 45.2) followed by blood vessel and lymphatic vessel invasion (Chi‐square: 43.6 and 40.0) had the highest prognostic value, whereas TCD (Chi‐square: 31.5) revealed a prognostic value quite similar to that of lymph‐node involvement (Chi‐square: 35.1). This prognostic relevance was still present in multivariate Cox regression analysis, showing that the determination of TCD provided an increase in prognostic information which significantly (p = 0.026) exceeded the information obtained by the combination of T‐stage and lymph‐node involvement. Our data suggest that TCD is a new prognostic parameter, especially in those gastric carcinomas in which lymph‐node involvement or vascular invasion are not present.
Type‐1 plasminogen activator inhibitor in human breast carcinomas
Authors: Reilly David , Christensen Use , Duch Mogens , Nolan Naimh , Duffy Michael J. , Andreasen Peter A. 
Published: February 2007

AbstractWe have investigated the occurrence of type‐1 inhibitor of plasminogen activators (PAI‐I) in human breast tumors. PAI‐I levels, measured by enzyme‐linked immunosorbent assay, were significantly higher in malignant breast carcinomas (n = 178) than in benign breast tumors (n = 25). The levels of PAI‐I were found to be correlated with those of urokinase‐type plasminogen activator (u‐PA). The presence of PAI‐I in tumor extracts was also demonstrated by immunoblotting analysis. Immunohis‐tochemical investigations by the use of monoclonal and polyclonal antibodies showed that PAI‐I was mostly localized in the tumor islands, associated with the tumor cells; in addition, it was present in vessel walls and in normal duct epithelia, but absent from the stroma. Analysis of RNA extracted from tumors by polymerase chain reaction revealed the presence of PAI‐I mRNA. We conclude that PAI‐I is present in human breast carcinoma cells, and that it is‐at least partially produced locally, either by the cancer cells or by other cells in the tumors. We have previously demonstrated that a high level of u‐PA in human breast carcinomas is associated with poor prognosis. These results, combined with our present findings, present 2 possibilities: either the cancer cells need PAI‐I in order to utilize the u‐PA‐mediated pathway of plasminogen activation for invasion and metastasis; or PAI‐I represents a defense mechanism against tumor invasion.