bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Mechanisms of Initial Dissociative Chemisorption of Oxygen on Transition‐Metal Surfaces
Authors: Nolan Peter D. , Wheeler M. Clay , Davis John E. , Mullins C. Buddie
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Stereochemistry of Zirconium and Hafnium Fluoro Complexes
Authors: Davidovich R. L.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Design of Constrained Analogues of Amino Acids and Their Incorporation in the Sequence of Substance P
Authors: Ayoub Mimoun , Brunissen Alie , Josien Hubert , Loffet Albert , Chassaing Gerard , Lavielle Solange
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Examples of Active Areas of Structure‐Based Design
Authors: Gubernator K. , Boehm H. J.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Novel Five‐ and Six‐ Membered Bisheterocyclic Systems from Dithiocarbamates and Related Compounds
Authors: Franco Santiago , Merchan Francisco L. , Merino Pedro , Tejero Tomas
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Polymer‐Assisted Solution Phase (PASP) Chemical Library Synthesis
Authors: Flynn Daniel L. , Devraj Rajesh V. , Naing Win , Parlow John J. , Weidner John J. , Yang Syaulan
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: From Olefin Cyclopropanation to Olefin Metathesis Through Catalyst Engineering: Recent Applications of Olefin Metathesis to Fine Organic Synthesis and to Polymer Chemistry
Authors: Noels A. F. , Demonceau A.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Whole blood flow cytometric measurement of NFATc1 and IL‐2 expression to analyze cyclosporine A‐mediated effects in T cells
Authors: Brandt Claudia , Liman Peter , Bendfeldt Hanna , Mueller Karin , Reinke Petra , Radbruch Andreas , Worm Margitta , Baumgrass Ria
Published: June 2010

The calcineurin inhibitor Cyclosporine A (CsA) is one of the crucial immunosuppressive drugs given after organ transplantation. The small therapeutic window of CsA generates the dilemma that efficient and toxic drug doses differ only slightly. Moreover, these threshold concentrations differ considerably between individuals; therefore, functional assays are urgently needed. We explored whether the transcription factor NFATc1, a direct as well as indirect target of CsA, can be used as a potential biomarker to determine the individual immunosuppressive activity of CsA. First, in isolated human T cells we showed that flow cytometry is practicable to measure NFATc1, the most abundant NFATc isoform in activated T cells. Second, for whole blood we developed a flow cytometric assay to determine in parallel the inducible transcription factor NFATc1 and the cytokine IL‐2 in stimulated T cells. We found that added CsA inhibits both the expression of NFATc1 and IL‐2 in T cells of stimulated whole blood samples with IC50 values of 200 and 150 nM, respectively. The intra‐ and inter‐assay variability was low, and clinical practicability was good. Further experiments have to demonstrate whether the parallel cytometric measurement of NFATc1 and IL‐2 in whole blood is a good predictor of individual CsA efficacy and toxicity in CsA‐treated patients. © 2010 International Society for Advancement of Cytometry.
The influence of the thymus on the development of transplanted mammary tumour in mice
Authors: Belyaev D. K. , Gruntenko E. V.
Published: June 2010

The influence of thymectomy and the grafting of additional thymuses on the development of syngeneic mammary tumour has been studied in high cancer C3H/He strains of mice. The effect on the development of the grafted tumour of replacement of the thymus of F1 hybrid mice (C3H/HexC57BL) by thymus derived from donors of the parental streins has also been investigated.

In C3H/He mice thymectomized on the 3rd day after birth the development of mammary tumour grafted at the age of 2 months was delayed. One or three additional syngeneic thymuses from 1‐month‐old donors grafted subcutaneously to C3H/He mice stimulated the development of grafted tumours, whereas inhibition of tumour development was observed in mice grafted with five additional thymuses.

The replacement of the thymus in F1 hybrid mice (C3H/HexC57BL) at the 5th day after birth by thymus of 5‐day‐old donors of low cancer C57BL strain led to the inhibition of mammary tumour grafted to mice at 2‐3 months of age, while the replacement of the hybrid thymus by that obtained from donors of the high cancer C3H/He strain had no inhibitory effect.

The data presented have been interpreted as evidence for genetically determined differences in the functional specificity of the thymus concerning its influence on malignant growth in high and low cancer strain mice. It is suggested that hereditary predisposition to malignant growth is, in particular, related to the functional properties of the thymus in high cancer strains of mice.
The origin of human embryo lung cells in culture: A comment on cell differentiation, in vitro growth and neoplasia
Authors: Franks L. M. , Cooper T. W.
Published: June 2010

The ultrastructure of cells derived from 15 human embryo lung culture lines, at 11 different transfer generations (2nd–19th) was examined, and compared with that of cells present in starting cell suspensions and explants. Differentiated epithelial cells were not seen after the second transfer generation. Two predominant cell types were present in all cultures. These cells were morphologically similar to endothelial cells and pericytes present in the initial explants. It is suggested that many tissue culture cell lines established from normal tissues may be derived from these cell types.

Since some differentiated tumour cells with recognizable tissue markers can be maintained in vitro, under similar culture conditions the “normal” cells must have similar metabolic pathways, and therefore may not be satisfactory control material for biochemical and other studies of normal and tumour cells. The ability of differentiated cells to become established in vitro seems to be associated with the development of neoplastic characters.
Analyse quantitative in vivodes réctions immunitaires dirigées contre les antigénes associés a des tumeurs murines solides
Authors: Donner M. , Oth D. , Vaillier D. , Burg C.
Published: June 2010

The dose‐response curves and the TD50 are considered to be biological characteristics of tumors. Further these parameters vary according to the immunological status of the host. By using the TD50 method, a quantitative in vivo determination has been made of immune reactions directed against tumor‐associated transplantation antigens (TATA) of three solid murine tumors. The intensity of the primary immune reaction is evaluated by the difference between the TD50 values in normal and immune‐depressed animals. On the other hand, the secondary immune response is estimated by the difference between the TD50 in normal and specifically immunized recipients.

According to these criteria, the results show that the intensity of the primary and secondary immune reactions cannot be compared from one tumor to another. For one tumor, the secondary reaction is quantitatively much greater than the primary reaction. For another tumor, the exact opposite is the case. These results suggest that there is no correlation between the primary and secondary immune responses and that they are quantitatively dependent upon multiple factors. The results are discussed in relation to the determination of antigenic strength of tumors.
The response of immunologically reconstituted mice to allogeneic skin or tumour grafts
Authors: Weston B. J. , Cheers C. , Carter R. L. , Leuchars E. , Wallis V. J. , Davies A. J. S.
Published: June 2010

A study has been made of cytological and histological changes in lymph nodes draining grafts of allogeneic skin or tumour. The two types of graft provoked mitosis of both thymus‐ and bone‐marrow‐derived lymphocytes; this activity was associated with reactive changes initially in the paracortex and then in germinal centrts and medullary cords. Grafts of allogeneic skin evoked two peaks of mitosis which declined rapidly as the graft was rejected. Transient mitotic activity also occurred in response to (control) syngeneic skin, coinciding with increased lymph‐node weight and some paracortical hyperplasia but (cf. changes found after allografting), other parts of the node did not respond. Allogeneic EL4 lymphoma cells gave rise to a greater and more rapid immunological response than did skin grafting. The mitotic response to the injected tumour cells failed, at least in the draining lymph nodes, long before death of the host due to progressive tumour growth. It is suggested that both the greater mitotic response, and its later failure, are related to the progressive growth of the tumour and to the everincreasing antigenic burden which such a tumour represents.
Inhibition of ascites tumor development by concanavalin a
Authors: Inbar Michael , Ben‐Bassat Hannah , Sachs Leo
Published: June 2010

The protein concanavalin A (Con. A) that binds to glucose or mannose‐like sites on the cell surface membrane, and glycoproteins from wheat germ and soybean that bind to N‐acetyl‐D‐glucosamine‐like sites and N‐acetyl‐D‐galactosamine‐like sites, respectively, agglutinate cells of the ascites form of a Moloney virus‐induced lymphoma (YAC) grown in vivo. Although YAC cells were agglutinated by all three agglutinins, only Con. A showed a marked toxic effect on YAC cells in vitro and in vivo. In vitro incubation with 125μMg Con. A for 24 h lysed 95% of the cells. Intraperitoneal injection of 1 mg Con. A at 1 h, 2 days and 5 days after intraperitoneal inoculation of 102 YAC cells into adult mice, resulted in an inhibition of tumor formation in 70%, 50% and 20% of the animals, respectively. The results indicate that activities essential for cell survival are associated with Con. A sites, but that most of these activities are not associated with sites for the wheat germ and soybean agglutinins.
Electron microscopical study of rowson‐parr virus infection in balb/c mice
Authors: Michaels L. , Rowson K. E. K. , Bird E. S.
Published: June 2010

The significant electron microscopic changes in the course of Rowson‐Parr virus infection in BALB/c mice are described. In the early splenomegaly there is active folding of cell membranes of reticulum cells of the spleen in germinal centres and red pulp. Type‐C virus particles are seen between the folds, but not budding from these cells. This change is interpreted as the localization of virus antigen prior to specific antibody production. Plasma cells are present in considerable numbers in the red pulp soon after. These changes persist to a lesser degree in the spleen throughout the period when it is of normal size. The cells constituting the lymphoma resemble other murine lymphomas and are also characterized by the frequent appearance of type‐C virus particles budding from their surfaces.

Electron microscopy of negatively stained centrifuged plasma was also carried out. In the first 4 days single scattered virus particles of typical murine oncogenic type are present, but these become agglutinated from the 5th day onwards. Perivascular mononuclear cell infiltrates are present in the kidneys after the 30th week. These are composed of plasma cells and reticulum cells with folded membranes, enclosing virus particles.

The lymphoma in RPV infection thus develops at the site of and following a prolonged period of immunological reaction to the virus.
Identity of the soluble ebv‐associated antigens of human lymphoid cell lines
Authors: Reedman Beverley M. , Pope J. H. , Moss D. J.
Published: June 2010

The reactions of human sera with antigens prepared from five human lymphoid cell lines were studied by immunodiffusion. Two major precipitation lines occurred with QIMR‐WIL antigens; one (S line) due to a soluble antigen and the other (F line) due to a sedimentable antigen. A close association in human sera of precipitins producing the S line with antibody to Epstein‐Barr virus (EBV) detectable by immunofluorescence (Henle test) and by complement fixation (CF) tests indicated a specific association of the S line with EBV, but the nature of the F line was not clarified. Soluble antigens prepared from five lymphoid cell lines (including Raji) contained at least one common identical heat‐resistant component, defined as the antigen giving the S line. The ease of detection of the S antigen in cell lines by immunodiffusion appeared to be related to the titre of the soluble EBV‐associated CF antigen, and the evidence suggested that the soluble CF and ID antigens were probably identical.
The combined action of rauscher leukemia virus and lactic dehydrogenase virus on mouse lymphatic tissue
Authors: Proffitt Max Rowland , Congdon C. C , Tyndall R. L.
Published: June 2010

Mice inoculated with animal‐passaged Rauscher leukemia virus contaminated with lactic dehydrogenase virus showed early gross and histological changes in their lymphatic tissues comparable to those in mice inoculated with lactic dehydrogenase virus alone. Some of the changes closely resembled those that have been ascribed to stress, which are mediated by corticosteroid hormones Except for early erythroblast activation, mice inoculated with a pool of animal‐passaged Rauscher leukemia virus derived from cell culture and not contaminated with lactic dehydrogenase virus did not undergo these changes. Most notable were the absence of early lymphocyte destruction in thymus‐dependent areas responsible for cell‐mediated immunity and the lack of significant immunoblast activation and proliferation in lymphoid germinal centers (humoral immune compartment).

The presence of lactic dehydrogenase virus in Rauscher leukemia virus pools or its addition to the uncontaminated pool resulted in an enhancement of the “erythro‐blastic reaction” associated with Rauscher disease, as indicated by an increase in spleen weight. There was also prominent diffuse and persisting hyperplasia of germinal center cells (immunoblasts and immunocytes) after lactic dehydrogenase virus was added to the uncontaminated Rauscher virus pool. Furthermore, the presence of the lactic dehydrogenase virus enhanced the immunosuppressive properties of Rauscher leukemia virus.

Two possibilities were considered to account for the enhancement of Rauscher disease by lactic dehydrogenase virus. First, by stimulating germinal center hyperplasia, the virus could supply greater numbers of target cells for Rauscher virus replication. Second, the depression of the cell‐mediated immune response by lactic dehydrogenase virus could prevent the inactivation of Rauscher virus particles, or tumor cells by lymphocytes.
Further studies on the mechanism of growth of a transplantable virus‐induced lymphoid tumour of mice
Authors: Croft C. J.
Published: June 2010

The nature of mitotic host cells observed in transplants of a virus‐induced lymphoid tumour of mice has been investigated. Evidence is presented indicating that they are stromal in nature and not tumour cells. Transplants of this tumour into neonatal or adult mice grow only by the proliferation of donor cells, and the cells of secondary tumours found in the spleens of mice bearing subcutaneously transplanted tumours are also derived from the cells inoculated. The role of the virus in the growth of this tumour is compared with that of the Rous sarcoma of chickens.
Properties of a murine sarcoma virus isolated from a tumor arising in an nzw/nzb f1 hybrid mouse. i. isolation and pathology of tumors induced in rodents
Authors: Gazdar Adi F. , Chopra Harish C. , Sarma Padman S.
Published: June 2010

A potent sarcoma virus was isolated after in vivo passage of a tumor arising spontaneously in a New Zealand White × New Zealand Black (B/ W) F1 hybrid mouse. Inoculation of the virus into mice, rats, hamsters, and Mastomys resulted in the rapid development of tumors at the sites of inoculation. The tumors induced in mice were sarcomas consisting of spindle cells and many inflammatory cells. Most tumors had a prominent angiomatous component. Tumor regressions occurred in some mice, while other tumors grew progressively, metastasized, and resulted in death. B/ W mice developed splenomegaly 4‐6 weeks after virus inoculation. The normal architecture of their spleens was completely destroyed and replaced by angiomatous tissue, fibrosis, and inflammatory changes. Virus‐induced tumors in hamsters consisted of undifferentiated polygonal cells. Virus‐induced tumors of rats and Mastomys consisted of thin‐walled blood vessels heavily infiltrated with polymorphonuclear leukocytes. Primary virus‐induced tumors in hamsters, rats, and Mastomys did not regress, but some transplanted hamster tumors regressed. Electron microscopy of virus‐induced and transplanted tumors revealed numerous type‐C virus particles morphologically similar to the murine leukemia‐sarcoma viruses. Tumor homogenates contained the group‐specific (gs) antigen of the murine leukemia‐sarcoma viruses.
Site selective cyclic amp analogues are antagonistic to estrogen stimulation of growth and proto‐oncogene expression in human breast‐cancer cells
Authors: Katsaros Dionyssios , Ally Shamsia , Cho‐Chung Yoon Sang
Published: June 2010

Cyclic AMP (cAMP) analogues that selectively bind to either one of the two binding sites of cAMP‐dependent protein kinase demonstrate a potent inhibition of the growth stimulated by estrogen in MCF‐7 human breast‐cancer cells in culture. The site‐selective analogues, which are more potent activators of protein kinase than the analogues studied earlier, exhibit growth inhibition at micro molar concentrations. Among the analogues tested, 8‐CI‐cAMP (Site I‐selective) and N6‐benzyl‐cAMP (Site 2‐selective) are the 2 most potent inhibitors, causing 40‐70% inhibition of the estrogen‐stimulated growth at 10‐20 μM concentrations with no sign of toxicity. 8‐CI‐cAMP (I μM) in combination with N6‐benzyl‐cAMP (0.5 μM) almost completely blocks estrogen‐stimulated growth, demonstrating synergism between the Site 1‐and Site 2‐selective analogues. The growth inhibition parallels an increase in the R11cAMP receptor protein with a decrease in the R1 receptor as well as a reduction of c‐myc and c‐ras oncoproteins, whereas growth inhibition by tamoxifen does not affect the levels of the cAMP receptor proteins or the c‐myc and c‐ras protein levels. Site‐selective cAMP analogues are antagonistic to estrogen stimulation of breast‐cancer cell growth through a mechanism different from that of tamoxifen.
Influence of cyclosporin a on growth of an acute T‐cell leukaemia in PVG rats
Authors: Thomson A. W. , Forrest E. H. , Smart Louise M. , Sewell H. F. , Whiting P. H. , Davidson R. J. L.
Published: June 2010

Our objective was to examine the effect of cyclosporin A (CsA; 25 or 12.5 mg/kg) on growth of an acute (Roser) T‐cell leukaemia in male PVG rats. The leukaemic blasts were shown (by immiunocytochemical analysis) to have a mature, T‐helpercell phenotype, i.e., OX‐19 (CD5)∓,W3/25 (CD4)∓,OX44∓MHC‐class I+, OX‐26+, corresponding to a population comprising 5% of normal rat medullary thymocytes. Animals received 20 × 102 viable tumour cells intramuscularly (day 0) and were given either CsA (25 or 12.5 mg/kg) or drug vehicle by gavage from day 0 or day 14, by which latter time leukaemic blasts normally appeared in the circulation. Administration of the higher dose of CsA from day 0 or day 14 significantly delayed the appearance of leukaemic cells in the peripheral circulation, whereas treatment with 12.5 mg/kg was without significant effect. CsA whole blood levels on day 17 were twice as high in leukaemic rats as in normal controls. Leukaemic infiltration of the spleen and the liver was reduced on day 17 after 25 mg/kg CsA, but no such effect was observed in lymph nodes or kidneys. A heterogeneous, host “reactive” cell population, which developed in response to the leukaemia, was inhibited by CsA, indicating that the effect of the drug was probably not mediated by host defence mechanisms. In CsA‐treated leukaemic animals, there was biochemical evidence of synergistic impairment of gtomerular and tubular function.
Biodistribution and tumour localization of a methotrexate‐monoclonal‐antibody 791T/36 conjugate in nude mice with human tumour xenografts
Authors: Pimm M. V. , Clegg Jane A. , Garnett M. C. , Baldwin R. W.
Published: June 2010

The blood kinetics and tumour localization of a conjugate of methotrexate (MTX) and MAb 79IT/36 were examined in nude mice with human tumour xenografts. The antibody moiety of the conjugate was detected by labelling with 125I and the drug moiety was assayed using a radioimmunoassay for methotrexate. After radio rodination, the drug moiety was co‐precipitable with the radiolabel when TCA or rabbit anti‐mouse IgG antiserum was used. Following i.v. injection, serum kinetics of both the antibody and the drug moieties of the conjugate were essentially similar, and the integrity of serum‐borne conjugate was confirmed by the co‐precipitation of radiolabel and drug. The radiolabelled antibody moiety of the conjugate localized in tumour xenografts, with 5‐7% of the injected dose being present per gram of tissue within 6 hr of injection, and the levels were maintained for up to 4 days. Analysis of tumour levels of the MTX moiety showed a progressive uptake over the 4‐day observation period with up to 4% of the injected dose being present per gram of tumour when the experiment was terminated. Parallel studies with free MTX showed rapid clearance from the blood and a maximum of 0.354b of the dose/g of tumour 30 min after injection. Control immunogiobulin conjugated to MTX did not show tumour localization of either the antibody or the drug moieties. These studies confirm that in vivo MTX remains bound to antibody in this type of drug antibody conjugate and demonstrate site‐specific targeting of this therapeutic agent.
Immortalization of a human colorectal adenoma cell line by continuous in vitro passage: Possible involvement of chromosome 1 in tumour progression
Authors: Paraskrva Christos , Finerty Susan , Powell Susan
Published: June 2010

A non‐tumorigenic epithelial cell line designated PC/AA, derived from a large pre‐malignant colorectal adenoma from a patient with familial polyposis coli (also referred to as hereditary adenomatosis of the colon and rectum) has became immortal in vitro. PC/AA has been passaged in vitro continuously for over A years and shows no signs of senescence. At early passage, PC/AA has a normal diploid karyotype but with late passage is showing signs of progression, becoming aneuploid and displaying signs of morphological transformation. Every cell examined of late‐passage PC/AA has an isochro‐mosome (Iq), and one other marker chromosome which is probably derived from an additional chromosome 8. The majority of cells examined have 48 chromosomes. Despite showing signs of progression in vitro, late‐passage PC/AA has remained non‐tumorigenic in athymic nude mice and retained morphological differentiation characteristics of colonic cells, in particular the ability to synthesize and secrete mucin. Two other cell lines derived from small adenomas did not become immortal in vitro and were also non‐tumorigenic in athymic nude mice. The isolation of an immortal pre‐malignant human epithelial cell line could prove invaluable in studies on human careinogenests and tumour progression. Our results, showing that only a large adenoma and no small adenomas have given rise to immortal cell lines, raise the possibility that the acquisition of in vitro immortality is associated with a relatively late stage in the adenoma‐carcinoma sequence. The possible involvement of chromosome I in tumour progression is discussed.
Correlation between viral dna load and serum anti p19 antibody concentrationtn symptomless human T‐lymphotropic virus type‐I (HTLV‐I)‐infected individuals
Authors: Morand‐Joubert Laurence , Mariotti Martine , Reed Donna , Petit Jean‐Claude , Lefrere Jean‐Jacques
Published: June 2010

In order to determine whether serum anti‐human T‐cell lymphotropic virus type I (HTLV‐I) antibody concentration is correlated with cellular viral DNA load, these 2 biological parameters were established in 22 symptomless HTLV‐I carriers. The proviral copy (PVC) number was determined through quantificative polymerase chain reaction. Specific antibody titers were determined by Western blot with the end‐point dilution method; the quantification of each antibody was performed through ScanGlot by determination of the peak height of each Western‐blot band. A positive correlation was observed between the PVC number and the titer of total antibodies. When the association between the peak height of each antibody and the PVC number was studied, a significant positive correlation was observed only with anti‐p 19. Further evaluation through follow‐up studies of symptomless HTLV‐I individuals is needed to clarify the value of anti‐HTLV‐l antibody titer as a predictor of disease progression. © 1995 Wiley‐Liss, Inc.
Smoking and cancer mortality among U.S. veterans: A 26‐year follow‐up
Authors: McLaughlin Joseph K. , Hrubsec Zdenek , Blot William J. , Fraumeni Joseph F.
Published: June 2010

On the 30th anniversary of the U.S. Surgeon General's report Smoking and Health, we present updated results from one of the original cohort studies that comprised the groundbreaking document. A 26‐year follow‐up of 248,046 U.S. veterans evaluating the risks of cigarette smoking revealed strong dose‐response effects between smoking and total cancer and a large number of cancer sites. Over 50% of cancer deaths among current smokers and 23% of cancer deaths among former smokers were attributable to cigarette smoking. These findings further demonstrate the large and unique role cigarette smoking plays in cancer etiology and the importance of smoking cessation to reduce this enormous public health burden. © 1995 Wiley‐Liss, Inc.
Effects of cytokine‐mediated modulation of nm23 expression on the invasion and metastatic behavior of B16F10 melanoma cells
Authors: Parhar Ranjit S. , Shi Yufei , Zou Minjing , Farid Nadir R. , Ernst Peter , Al‐Sedairy Sultan T.
Published: June 2010

The molecular mechanisms of tumor invasion and metastasis are yet to be fully elucidated. A potential tumor‐metastasis‐suppressor gene nm23 has been described in certain rodent and human tumors. In the present study, we examined the potential anti‐invasive and anti‐metastatic effect of nm23 gene in B16F10 cells, a malignant murine melanoma cell line. Transfection of nm23 gene into B16F10 melanoma ceils resulted in significant suppression of the invasiveness and metastatic ability of melanoma cells and significantly enhanced the survival of tumor‐bearing mice. B16F10 melanoma cells transfected with nm23 produced significantly less soluble ICAM‐I and were more susceptible to LAK‐cell‐mediated cytotoxicity. Co‐culture of B16F10 melanoma cells with IL‐2 had no effect on nm23 expression, whereas treatment with PGE2, TNF‐α and IFN‐γ resulted in down‐regulation of nm23 expression. Concomitantly, in vivo treatment with TNF‐α or IFN‐γ in experimental mice increased pulmonary metastases and lowered the overall survival period, as compared with IL‐2 treatment alone. These results provide evidence that nm23, in addition to its anti‐metastatic function, could also be involved in modulating tumor‐target‐structure expression, in down‐regulating invasive potential and in production of soluble intracellular adhesion molecules. The down‐regulation of nm23 by TNF‐α, IFN‐γ and particularly by PGE2 warrants re‐examination of current immunotherapeu‐tic protocols and of the role played by PGE2 in tumor progression. © 1995 Wiley‐Liss, Inc.
Mitogenic effect of the 15‐kDa gross cystic disease fluid protein (GCDFP‐15) on breast‐cancer cell lines and on immortal mammary cells
Authors: Cassoni Paola , Sapino Anna , Haagensen Darrow E. , Naldoni Carlo , Bussolati Gianni
Published: June 2010

The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15‐kDa glycoprotein (GCDFP‐15), is presently unknown. We have added GCDFP‐15 to cell culture medium and tested its effect on proliferation of 4 human breast‐cancer cell lines (MCF7, BT474, MDA‐MB231 and T47D) and a “normal” human immortal breast‐cell line (MCF10A). These breast‐cell lines showed a mitogenic response to GCDFP‐15 (10 μ/ml). GCDFP‐15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA‐MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto‐regulatory effect of endogenous GCDFP‐15 synthesized by the T47D cells. GCDFP‐15 was ineffective on 2 colon‐cancer cell lines (HT29 and NIC‐H7I6), on the IMR32 neuroblastoma cell line and on the NIC‐H209 small‐cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP‐24) was tested, following the same experimental design, on the 5 breast‐cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP‐15 observed in this study in both “normal” and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP‐15 in breast‐cancer progression should be considered. © 1995 Wiley‐Liss, Inc.
Modulation of cellular chemoresistance in keratinocytes by activation of different oncogenes
Authors: Sanchez‐Prieto Ricardo , Vargas Juan Antonio , Carnero Amancio , Marchetti Elena , Romero Jesus , Durantez Alberto , Lacal Juan Carlos , Cajal Santiago Ramon Y
Published: June 2010

Response to chemotherapeutic agents in malignant tumors depends on many factors, most of which are as yet unknown. We investigated the correlation between the activation of different oncogenes and protein‐kinase‐C(PKC) modulation, and the cytotoxicity of some of the most widely used anti‐cancer drugs. We transformed the murine keratinocyte cell line PAM 212, with different oncogenes (v‐H‐ras, v‐myc and adenovirus El a) and a mutant p53 suppressor gene (mp53). The cytotoxic effect of cisplatin (CDDP), doxorubicin(DOX) and vincristine (VCR), together with the concomitant action of modulators of PKC, TPA and staurosporine were evaluated by the crystal‐violet method, thymidine incorporation and flow cytometry. We report that (a) the oncogene v‐H‐ras induces resistance to CDDP (> 50%), DOX (> 25%) and VCR (> 20%); (b) the E l a oncogene induces only resistance to VCR (>40%) and marked sensitivity to CDDP and DOX; (c) the mp53 oncogene induces more resistance to VCR and insignificant resistance to the other drugs; and (d) activation of PKC by TPA increases the resistance to VCR and DOX in cells transformed by the v‐H‐ras, while it significantly increases the lethality with CDDP of the E l a‐transformed cells. Staurosporine increases the cytoxicity of all the drugs, especially in the E l a‐transformed keratinocytes. In the flow‐cytometry analysis, the percentage of BUdR incorporation was related to sensitivity to anti‐cancer drugs. © 1995 Wiley‐Liss, Inc.
Reduction of translation initiation factor 4E decreases the malignancy of ras ‐transformed cloned rat embryo fibroblasts
Authors: Graff Jeremy R. , Boghaert Erwin R. , De Benedetti Arrigo , Tudor Dianna L. , Zimmer Constance C. , Chan Shung Kai , Zimmer Stephen G.
Published: June 2010

Expression of the T24ras oncogene induces malignancy (tumor growth, invasion and metastasis) in cloned rat embryo fibroblasts (CREF T24). In CREF T24, the rate of phosphorylation of eukaryotic translation initiation factor 4E (elF‐4E) is increased, resulting in increased protein synthesis rates. We have recently shown that reducing the protein levels of elF‐4E in CREF T24 (AS4E line) markedly decreases soft‐agar colonization, increases tumor latency periods and increases tumor doubling times without significantly altering monolayer growth. In this study, cells with reduced elF‐4E had delayed and reduced invasiveness and decreased experimental metastasis. Furthermore, reduced elF‐4E levels correlated with decreased expression of the metastasis‐associated 92‐kDa collagenase type‐IV and exon‐6 variants of the CD44 adhesion molecule [CD44(6v)]. Reduced elF‐4E levels correlated inversely with increased levels of the putative metastasis‐suppressor protein nm23. Cell lines established from AS4E tumors and lung metastases exhibited increased levels of elF‐4E protein and protein synthesis rates compared to the AS4E line. Tumor‐derived AS4E had the shortened tumor latency periods of CREF T24 but displayed the slow tumor‐growth rates of AS4E. Tumor‐derived AS4E exhibited the metastatic capacity of CREF T24 controls. Furthermore, tumor‐ and lung‐nodule‐derived AS4E expressed levels of CD44 (6v) and the 92‐kDa collagenase type IV comparable to CREF T24 and displayed reduced levels of nm23 relative to AS4E. These results demonstrate that elF‐4E is an important effector molecule involved in oncogenic p2lras‐induced malignant transformation. © 1995 Wiley‐Liss, Inc.
Growth properties of a human melanoma cell line are altered by adeno‐associated parvovirus type 2
Authors: Bantel‐Schaal Ursula
Published: June 2010

The adeno‐associated parvoviruses (AAV) are known for their oncosuppressive activity. This report shows that infection of the human melanoma cell line MKr with AAV‐2 leads to chromosomal integration of the viral DNA. The resulting cultures show decrease of saturation density and reduction in their ability to form colonies from single cells and thus to resemble normal cells. After single‐cell cloning they may give rise to growth‐arrested, terminally differentiating large, multinucleated cells with dendrite‐like extensions, large nucleoli and the ability to synthesize melanin pigment. In cultured melanoma cells, melanin synthesis is correlated with cellular senescence, and since senescent cells cease to proliferate and withdraw from the cell cycle, the apparent induction of growth arrest and terminal differentiation in malignant cells by AAV may provide one explanation for the anti‐neoplastic activity of these viruses. © 1995 Wiley‐Liss, Inc.
Lung adenocarcinoma and indicators of asbestos exposure
Authors: Mollo Franco , Pira Enrico , Piolatto Giorgio , Bellis Donata , Burlo Paola , Andreozzi Armando , Bontempi Silvano , Negri Eva
Published: June 2010

A case‐control study was carried out on 145 male lung‐cancer patients diagnosed at autopsy and 178 controls, in order to investigate the relationship between asbestos exposure and the cell type of pulmonary carcinoma. Adenocarcinomas (AD) were individually matched with other cell types and with controls. The relative risk (RR) of developing AD in relation with lung asbestos body (AB) content as the exposure indicator was calculated by using logistic‐regression analysis for matched sets. Two cutoff levels, 1,000 and 10,000 asbestos bodies per gram dry weight (AB/gdw), were used in the analysis. In addition, AB counts were treated as a continuous variable (log AB + 1). A significant association was found between AD and asbestos exposure, using levels and logarithmic transformation. However, an association of asbestos exposure with cell types other than AD could not be ruled out. © 1995 Wiley‐Liss, Inc.
Circulating gangliosides of breast‐cancer patients
Authors: Wiesner Douglas A. , Sweeley Charles C.
Published: June 2010

Gangliosides were isolated from the sera of recently diagnosed breast‐cancer patients and from individuals who were apparently free of disease. Quantitative and qualitative analyses were carried out by 2‐dimensional high‐performance thin‐layer chromatography and gas chromatography. The locations of isolated gangliosides on thin‐layer chromatograms were determined by visualization with resorcinol, and each spot was quantified by digital image densitometry. The ganglioside profiles of cancer patients were compared to those of the control group, revealing a significant increase in total lipid‐bound sialic acid and a specific increase in polysialogangliosides in the patients with breast cancer. Furthermore, an increase was noted in the ratio of gangliosides of the b‐series biosynthetic pathway over those of the a‐series in the cancer sera, as compared to the controls. Gas chromatographic analysis of the peracetylated methanolysis mixtures derived from the total ganglioside fraction of cancer patients supported the HPTLC data, with an increase in total sialic acid, galactose, and sphingosine residues. No unusual gangliosides were found in the mixture from breast‐cancer patients. © 1995 Wiley‐Liss, Inc.
Regional variations of urokinase‐type plasminogen activator in human colorectal cancer: A quantitative study by image analysis
Authors: Tan Kevin , Powe Desmond G. , Gray Trevor , Turner David R. , Hewitt Robert E.
Published: June 2010

Qualitative histological studies in the distribution of urokinase‐type plasminogen activator (uPA) in human colorectal carcinomas have been well documented. However, to our knowledge the histological distribution of this enzyme has not been quantified in any tumour. For the present image analysis study, uPA was demonstrated in sections of human colorectal cancer using immunoperoxidase technique. A total of 9 colorectal carcinoma cases were used, in which 132 regions were analysed. Within each region, staining intensity measurements were made at evenly spaced intervals. Samples of normal mucosa from 6 cases were also studied. Enzyme levels were assessed with staining intensity measurements. For each section, a negative control section was included, in which the primary antibody was omitted. Staining for uPA was quantified for each region in the test section, and the measurement for the corresponding region of the negative control was then subtracted. The enzyme uPA was localised more at the tumour edge than in the tumour centre or distant host tissue. These differences were highly significant (p < 0.0001). There was also a highly significant difference in staining intensity when tumour regions adjacent to pushing edge were compared with those adjacent to infiltrating edge (p < 0.0001). Infiltrating tumours showed stronger staining for uPA than tumours with pushing edges. Since invasive activity is thought to be maximal at the edge of the tumour, localisation of uPA at this site is consistent with the role of this enzyme in the process of tumour invasion. © 1995 Wiley‐Liss, Inc.
Modulation of E‐cadherin expression and morphological phenotype in the intravascular component of adenocarcinomas
Authors: Cowley Gerard P. , Smith Mark E. F.
Published: June 2010

E‐cadherin is a morphoregulatory epithelial cell/cell adhesion molecule whose loss from carcinomas probably contributes to a more invasive tumour phenotype. Employing an immunohisto‐chemical technique on 25 adenocarcinomas (8 from stomach, 10 breast, 7 colon) we compared E‐cadherin expression and tumour morphology of carcinoma that had invaded vascular spaces with that of extravascular carcinoma, both in primary tumours and in their lymph node metastases. In 40% of cases either at the primary site, in the lymph node metastasis or at both sites, E‐cadherin levels were higher in the often tiny intravascular tumour compartment than in the adjacent and much larger extravascular tumour compartment. In no tumour was the highest area of E‐cadherin expression present within the extravascular compartment. Increases in the differentiation and cohesion of intravascular tumour occurred in 16% and 20% of cases, respectively. In 3 of 4 cases showing increased differentiation, but in only 1 of 5 cases showing increased cohesion, these morphological changes were associated with increased intravascular E‐cadherin levels. © 1995 Wiley‐Liss, Inc.
Plasma levels of the atherogenic amino acid homocysteine in postmenopausal women with breast cancer treated with tamoxifen
Authors: Anker G. , Lonning P. E. , Ueland P. M. , Refsum H. , Lien E. A.
Published: June 2010

Long‐term treatment of breast‐cancer patients with the anti‐oestrogen tamoxifen has been found to be associated with reduced cardiovascular mortality. Plasma homocysteine is an independent risk factor for atherosclerotic disease, and its level is determined by folate and cobalamin status, and possibly also by oestrogen status. We measured the effect of tamoxifen on plasma homocysteine, serum cholesterol, serum cobalamin and serum and erythrocyte folate in 31 post‐menopausal women with breast cancer. The plasma homocysteine level was decreased by a mean value of 29.8% after 9–12 months and by 24.5% after 13–18 months of treatment. Tamoxifen suppressed serum cholesterol by mean values varying between 7.2% and 17.6% after 3 to 19 months of treatment. There was no correlation between changes in plasma homocysteine and serum cholesterol. These findings suggest that the homocysteine‐lowering effect of tamoxifen may contribute to the reduction of cardiovascular mortality observed in patients on adjuvant therapy with tamoxifen. © 1995 Wiley‐Liss, Inc.
Expression of tissue‐type transglutaminase correlates positively with metastatic properties of human melanoma cell lines
Authors: van Groningen Jan J. M. , Klink Steve L. , Bloemers Henri P. J. , Swart Guido W. M.
Published: June 2010

In this study the relationship between tissue‐type transglutaminase (TGase2) activity and the propensity to metastasize was investigated in human melanoma cell lines with different metastatic behavior. TGase2 catalyzes an acyl‐transfer reaction between peptide‐bound glutamine residues and primary amines, including the ε‐amino group of lysine residues. Northern‐blot analysis demonstrated that TGase2 RNA‐expression (3.7 kb) was elevated in highly metastatic cell lines (MV3 and BLM) as compared to weakly metastatic ones (I F6 and 530). Immunopre‐cipitation and enzyme assays of TGase2 showed that the differential expression at the mRNA level was also reflected at the protein level. These findings reveal a positive relation between the expression of TGase2 and the metastatic properties of the human melanoma cell lines. © 1995 Wiley‐Liss, Inc.
E‐selectin‐mediated dynamic interactions of breast‐and colon‐cancer cells with endothelial‐cell monolayers
Authors: Tözeren Aydin , Kleinman Hynda K. , Grant Derrick S. , Morales David , Mercurio Arthur M. , Byers Stephen W.
Published: June 2010

The molecular mechanisms involved in the dynamic interaction of human breast carcinoma cells with the endothelial cell lining of lymphatic vessels and post‐capillary blood venules are largely unknown. In the present study, laminar flow assays were used to investigate the ability of various normal breast cells and of breast‐ and colon‐tumor cells to adhere to human umbilical cord endothelial cell monolayers. MCF‐10A breast, MCF‐7 and T‐47D breast‐carcinoma and clone A, RKO, and HT‐29 colon‐carcinoma cells accumulated and rolled, in the presence of flow, on tumor necrosis factor (TNF)‐stimulated but not on unstimulated endothelial cell monolayers. Non‐tumor and tumor cells continued to form transient adhesions with TNF‐stimulated endothelial cells even when the flow rate was increased to levels found in arteries. Incubation of TNF‐stimulated endothelial cells with an E‐selectin‐specific monoclonal antibody (MAb) partially or completely inhibited dynamic interactions and diminished adhesion strength, whereas integrin β1‐ and integrin α6‐specific MAbs had no effect. A set of highly invasive breast‐carcinoma cells (MDA‐231, BT‐549, HS‐578t) neither adhered to nor rolled on resting or TNF‐stimulated endothelial cell monolayers. However, after 5 min of static incubation, a fraction of these cells attached strongly to resting and TNF‐stimulated endothelial cells and this static adhesion could not be blocked by an E‐selectin‐specific monoclonal antibody. Our results suggest that E‐selectin is a major homing receptor in the metastasis of some breast and colon cancers. © 1995 Wiley‐Liss, Inc.
Perspectives of data analysis of enzyme inhibition and activation, part 4: Equations for calculation of constants of enzyme activation and inhibition
Authors: Krupyanko Vladimir I.
Published: June 2010

Equations for calculation of constants of enzyme activation and nontrivial types of enzyme inhibition, which are not reported in the literature, have been deduced. Examples of using these equations are also presented. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:145–154, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20316
Free radical–scavenging activity and DNA damaging potential of auxins IAA and 2‐methyl‐IAA evaluated in human neutrophils by the alkaline comet assay
Authors: Salopek‐Sondi Branka , Piljac‐Žegarac Jasenka , Magnus Volker , Kopjar Nevenka
Published: June 2010

Auxins, of which indole‐3‐acetic acid (IAA) is the most widespread representative, are plant hormones. In addition to plants, IAA also naturally occurs in humans in micromolar concentrations. In the presence of peroxidase, indolic auxins are converted to cytotoxic oxidation products and have thus been proposed for use in gene‐directed enzyme/prodrug tumor therapy. Since data on the genotoxicity of IAA and its derivatives are not consistent, here we investigate the early DNA damaging effects (2‐h treatment) of the auxins, IAA, and 2‐methyl‐indole‐3‐acetic acid (2‐Me‐IAA) by the alkaline comet assay and compare them with their free radical–scavenging activity measured by the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay. Human neutrophils are chosen as the test system since they possess inherent peroxidase activity. The results of the comet assay indicate an increase in DNA damage in a dose‐dependent manner up to 1.00 mM of both auxins. Generally, IAA applied in the same concentration had greater potential to damage DNA in human neutrophils than did 2‐Me‐IAA. The genotoxicities of the two examined auxins are negatively correlated with their antioxidant activities, as measured by the DPPH assay; 2‐Me‐IAA showed a higher antioxidant capacity than did IAA. We assume that differences in the molecular structure of the tested auxins contributed to differences in their metabolism, in particular, with respect to interactions with peroxidases and other oxidative enzymes in neutrophils. However, the exact mechanisms have to be elucidated in future studies. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:165–173, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20323