bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of pregnancy and lactation on serum and breast fluid estrogen levels: Implications for breast cancer risk
Authors: Petrakis Nicholas L. , Wrensch Margaret R. , Ernster Virginia L. , Midce Rei , Murai James , Simberg Nicklas , Sirreri Pentti K.
Published: February 2007

We investigated estrogen (estrone and estradiof) levels in serum and in nipple aspirates of breast fluid in relation to reproductive and menopausal characteristics in 104 normal women. In general, breast fluid and serum estrogen levels were not correlated and breast fluid estrogen levels were approximately 5 to 45 times higher than serum levels. Serum estrogen levels were lower in post‐menopausal than in premenopausal women. In contrast, breast fluid estrogen levels were approximately the same in pre‐ and post‐menopausal women. Breast fluid estrogen mean levels were lower in premenopausal parous women than in nulligravidous or nulliparous women whereas serum estrogen levels did not differ in these 3 groups. Breast fluid estrogen levels were positively correlated with months since last birth or since last breastfeeding. Estrogen levels were low in nipple aspirates of breast milk but gradually increased in breast fluid of non‐lactating women over a period of several years after cessation of lactation. Serum estrogen levels did not increase with months since last breast‐feeding. We were unable to evaluate the postpartum effect of pregnancy without lactation due to the small numbers of these subjects. The high concentrations of estrogen in breast fluid and the absence of a relationship to serum estrogen levels may explain why prior serum studies have I failed to link variations in serum estrogens with breast cancer risk. The prolonged low levels of breast fluid estrogens following full‐term birth and lactation may, in part, provide a mechanism by which parity reduces breast cancer risk.
Immunochemical characterization and radioimmunometric petection of molecules shed by human ovarian cancer
Authors: Leoni F. , Bast R. C. , Canevari S. , Menard S. , Soper J. T. , Colnaghi M. I.
Published: February 2007

Monoclonal antibodies (MAbs) OC125, MOv2 and MOv8 recognize the CA125, CAMOv2 and CAMOv8 epitopes, respectively, which are associated with human ovarian carcinomas and are shed by these tumors. The biochemical analysis of the recognized antigens and epitopes has been performed to investigate the possibility of exploiting their expression, if any, on the same molecules. Cross‐competition experiments clearly indicated that the 3 epitopes are distinct. Biochemical analysis was performed on a cyst fluid from an ovarian cystadenoma. Heat treatment and periodate oxidation indicated that CAMOv2 and CAMOv8 are saccharidic and suggested that CA125 is a conformational epitope to which both saccharides and the protein backbone could contribute. By gel‐filtration chromatography CA125 activity was eluted into 2 peaks of high molecular weight, whereas CAMOv2 and CAMOv8 activities were associated with a single broad peak which included CA125‐positive fractions. Isopycnic centrifugation showed that CA125, CAMOv2 and CAMOv8 carrying molecules had the same high density (1.46 g/ml) in the first peak, whereas CA125 molecules had a lower density (1.41 g/ml) in the second peak. Double‐determinant immunoradiometric assays, carried out using different combinations of the MAbs, indicated that in the cyst fluid molecules expressing both CAMOv2 and CAMOv8 could be detected, whereas CA125 was carried by different molecules. CAMOv2 and CA125 could however be expressed on the same molecule in 2 out of 9 ascitic fluids from ovarian carcinoma patients. Taken together, these data indicate that CA125 and CAMOv2‐CAMOv8 were only occasionally expressed on the same molecules. Therefore, the use of the CA125‐CAMOv2 combination could not increase the sensitivity achievable by using each respective simultaneous immunoradiometric assay.
A classification scheme for childhood cancer
Authors: Birch Jillian M. , Marsden Henry B.
Published: February 2007

The International Agency for Research on Cancer (IARC) is sponsoring a worldwide study of childhood cancer incidence. Cancers in children are highly specific and differ in many ways from cancers found in adults. Data for the international study will be presented according to the classification scheme described below which has been devised specifically for use with paediatric cancers. The features of this scheme are: (I) it is based on the International Classification of Diseases for Oncology (ICD‐O); (2) diagnostic groups are defined mainly in terms of morphology; (3) the common types of childhood cancer are individually specified; (4) certain other rare conditions of interest are distinguished; (5) it provides for flexibility of data presentation with respect to amount of detail; (6) all possible combinations of ICD‐O morphology and topography codes are included; and (7) the maximum number of codes has been allocated to specific categories. There is a great need for standardization in the classification of childhood cancers and we propose that the scheme be used for presentation of incidence data for results of aetiologicaf and other related studies of cancer in children.
Cellular immunity changes caused by LDH virus: Analogy with observations on neuroblastoma‐bearing mice
Authors: Leclercq Georges , Willems Jean , Heremans Hubertine , Coutelier Jean‐Paul , Billiau Alfons , Joniau Marcel
Published: February 2007

Evidence is presented that LDH virus infection of mice results in drastic changes in several immune activities. Serum IFN titer and splenic NK activity are increased during the acute phase of infection. NK stimulation is mediated by IFN‐α,β since injection of an antibody against murine IFN‐α,β is able to abolish the effect. IL‐2 production is inhibited throughout the study period following injection of LDH virus (14 days), although a partial recovery is observed during the second week. Similarly, IL‐2 receptor expression and MLC responsiveness are suppressed. This suppression lasts for 2 and 7 days respectively after injection. Addition of recombinant IL‐2, but not of indomethacin, to the MLC cultures restores the proliferation rate. Not only proliferation but also cytotoxic cell generation in MLC is diminished during the first week after LDH virus injection. Again, this response is normalized at day 14. Additional observations indicate that LDH virus is present in murine neuroblastoma. This explains some of the previously described effects of this tumor on the cellular immune system of the host.
Effects of a single injection of anti‐asialo GM1 serum on natural cytotoxicity and the growth of a regressive colonic tumor in syngeneic rats
Authors: Shimizu T. , Pelletier H. , Hammann A. , Olsson N. O. , Martin M. S. , Martin F.
Published: February 2007

The REGb tumor cell line is a cloned variant of the DHD‐K12 cell line, established from a colon carcinoma chemically induced in the rat. Unlike the parent DHD‐K12 cell line, or other clones, which give progressive tumors when inoculated to the syngeneic rat, REGb cells produce tumors which regress in 3 to 5 weeks and never cause metastasis. In order to explore the role of natural killer (NK) cells in REGb tumor regression, each rat was given one injection of anti‐asialo GMI (anti as GMI) serum, a known inhibitor of NK activity. This injection was done 24 hr before REGb cell challenge. This injection significantly depressed the in vitro cytotoxicity of peripheral blood lymphocytes on REGb cells for 2 weeks. REGb tumors grew larger and regressed later in the treated animals than those in the controls. Furthermore, a progressive or recurrent tumor was observed in 4 out of 10 treated rats, giving lung and/or lymph‐node metastases in 2 cases. Immunohistological study of the cells infiltrating the REGb tumors in control and treated animals showed a decrease number of as GMI + and OX8+ lymphocytes, presumably NK cells, after anti‐as GMI treatment. An increase in number of macrophages was demonstrated in the progressive tumors of treated animals. These results suggest that NK cells play an important role in the initial stage of the regression TSb tumors in untreated syngeneic rats.
Differential expression of collateral sensitivity or resistance to cisplatin in human bladder carcinoma cell lines pre‐exposed in vitro to either X‐irradiation or cisplatin
Authors: Bedford Philip , Shellard Sharon A. , Walker M. Claire , Whelan Richard D. H. , Masters John R. W. , Hill Bridget T.
Published: February 2007

Two sublines were derived from a human bladder carcinoma continuous cell line (RTI12‐P), one by exposure to fractionated X‐irradiation (RTI12‐DXR8) and the other by continuous exposure to cisplatin (RTI12‐CP). RTI12‐DXR8 cells were 1.6‐ to 2‐fold more sensitive to cisplatin and 2 analogues, carboplatin and iproplatin, compared with the parental line, whereas RTI12‐CP cells were 1.6‐ to 2.8‐fold more resistant to these agents. Uptake of 195mcisplatin was elevated 1.4‐fold in RTI12‐DXR8 cells compared with RTI12‐P cells whereas uptake into RTI12‐CP cells was similar to that of the parental line. Binding of 195mcisplatin to DNA was similar in all 3 lines. Levels of reduced glutathione were significantly elevated in RTI 12‐CP cells and significantly reduced in RTI12‐DXR8 cells compared with the parental cells. In addition, activities of glutathione reductase and glutathione peroxidase were higher in RTI12‐CP cells than in the parental cells whereas the activity of glutathione‐S‐transferase was similar in all 3 cell lines. A 2.5‐fold greater induction of DNA‐DNA interstrand cross‐links occurred in RTI12‐DXR8 cells compared with the parental line, whereas crosslinking in RTI12‐CP cells, whilst initially similar to that seen in RTI12‐P cells, was significantly elevated at later times. These findings suggest that mechanisms associated with the expression of resistance and collateral sensitivity to cisplatin may differ.
DNA cytometry and cytology by quantitative fluorescence image analysis in symptomatic bladder cancer patients
Authors: Bass Rebecca A. , Hemstreet George P. , Honker Nancy A. , Hurst Robert E. , Doggett Reuben S.
Published: February 2007

A semi‐automated quantitative fluorescence image analysis (QFIA) technique was developed with the Leitz TAS‐Plus to detect bladder cancer using hyperploidy in urinary cells. Absolute nuclear fluorescence intensity (ANFI) (emission at 540 nm with excitation at 436 nm) of individual acridine‐orange‐stained cells was quantitated using (1) QFIA and (2) simple filter microspectrofluorophotometry (SFM). Both methods employed an internal phosphor particle standard which, when once calibrated against the DNA content of normal cells, obviates the necessity of routinely calibrating against normal cells in each sample. Results of SFM and QFIA were compared with routine Papanicolaou (Pap) cytopathology, using histopathology as the diagnostic standard in 272 samples from 67 symptomatic patients. The sensitivities for detecting low‐grade transitional‐cell carcinoma were 86% for SFM, 76% for QFIA, and 33% for Pap cytology. QFIA and SFM were significantly more sensitive at detecting bladder cancer than was Pap (0.0 > p > 0.001). Comparison of sensitivity obtained with blalder washings and urine samples showed that non‐invasively obtained urines can be used. ANFI also detected recurrent and precancerous bladder lesions and kidney, ureter, and prostate lesions. This approach may prove generally useful in quantifying biochemical and immunological probes and should be broadly applicable as a research tool for studying the relationship of biochemical markers in the pathogenesis of disease and as a test for cancer control.
Urine estrogens and breast cancer risk factors among post‐menopausal women
Authors: Trichopoulos Dimitrios , Brown James , Macmahon Brian
Published: February 2007

Creatinine‐adjusted levels of estrone, estradiol and estriol were determined in overnight urine specimens from 220 post‐menopausal women, aged 54 to 66 years, from Boston (121 women) and Athens (99 women). The associations of individual and total estrogens with various characteristics of the women (age at menopause, years since menopause, parity, age at menarche, schooling, height, weight, tobacco smoking and alcohol drinking) were studied by multiple regression procedures, to explore possible relationships and evaluate their compatibility with the descriptive epidemiology of female breast cancer. Weight was consistently and significantly related to higher levels of total estrogens and of each individually; the pattern of these associations was similar in American and Greek women, suggesting that the known qualitative differences in nutrition between the two groups of women are not important modifiers of the associations between weight and estrogens. Estrogen levels in these post‐menopausal women were about 40% of the corresponding follicular levels among teen‐age women. They did not decrease with age. There were suggestive but non‐significant negative associations between estrogen levels on the one hand, and parity and age at menarche on the other. There was no consistent association of estrogen levels with alcohol consumption. The data provide only modest support for the hypothesis that estrogens are important in breast cancer etiology.
Tobacco smoking, occupational exposure and bladder cancer in Argentina
Authors: Iscovich J. , Castelletto R. , Estè J. , Muñoz N. , Colanzi R. , Coronel A. , Deamezola I. , Tassi V. , Arslan A.
Published: February 2007

The highest rate for bladder cancer in Latin America has been reported from La Plata, Argentina. A case‐control study was carried out to investigate the reasons for this high rate. A total of 117 cases, 117 hospital controls and 117 neighbourhood sex‐ and age‐matched controls were interviewed regarding their smoking and drinking habits and occupational exposures. Cigarette smoking and coffee drinking were identified as the major risk factors, and a significant association was also found for truck and railway drivers and for oil refinery workers. The relative risks for male smokers who ever smoked cigarettes vs. non‐smokers was 4.3 (95% Cl: 1.9–10.3). The risk associated with black tobacco cigarettes was 2–3 times higher than that of blond cigarettes. For male ex‐smokers the risk after 5 years of no smoking is less than one third of that of current smokers. The RR for drinking coffee was 2.4 (95% Cl: 1.4–4.4) after adjusting for the effects of tobacco smoking, and the risk increased with the number of cups per day. No association was found with the use of saccharine.
Reproductive history and breast cancer in a population of high fertility, Costa Rica, 1984–85
Authors: Rosero‐Bixby Luis , Oberle Mark W. , Lee Nancy C.
Published: February 2007

The relationship between breast cancer and women's reproductive history in Costa Rica was analyzed using logistic regression methods on data from 171 breast cancer cases and 826 population‐based controls aged 25–58 years. The risk of breast cancer in nulliparous women under age 45 was 3 times that for parous women in the same age group. Women over 44 years of age with a parity greater than 4 had a risk of breast cancer of 0.3 compared to women of the same age but with a parity of 1–4. Neither breast‐feeding nor birth interval showed an overall association with breast cancer independent of parity. Women with early age at first birth had a lower relative risk of breast cancer than women aged 20–24 at first birth, but only in two subgroups—women aged 45 and over and women with parity 1–4. Women without a completed pregnancy in the last 20 years had an elevated relative risk. However, results are not conclusive because some information is probably distorted by recall errors. Declines in fertility rates in the 1960s and 1970s may result in an increase of 30% in breast cancer incidence in Costa Rica between 1980 and the year 2000, according to the relative risks found in this study. In contrast, the effect of childlessness will probably not produce significant changes in national breast cancer trends.
Mother‐to‐child transmission of human T‐cell leukemia virus type I (HTLV‐1): A fifteen‐year follow‐up study in Okinawa, Japan
Authors: Kusuhara Koichi , Sonoda Shunro , Takahashi Kazuo , Tokugawa Ken , Fukushige Junichiro , Ueda Kohji
Published: February 2007

Okinawa prefecture is one of the endemic areas for adult T‐cell leukemia/lymphoma (ATLL) in Japan. In this study, 2,013 serum specimens drawn serially over a period of 15 years (1968–1983) from 311 mother/child pairs in Okinawa were tested for antibodies to human T‐cell leukemia virus type 1 (HTLV‐1) by enzyme‐linked immunosorbent assay and by indirect Immunofluorescence. The prevalence rate of HTLV‐1 antibodies was 20.9% (65 cases) in the mothers and 3.2% (10 cases) in the children. Of the 65 seropositive mothers, 10 (15.4%) had seropositive children. This study revealed a significant difference between the prevalence rates of HTLV‐1 antibodies in mothers and children. In addition, children born to seropositive mothers had acquired their HTLV‐1 antibodies by the age of 3 years, and were still seropositive at the age of 18 years. No initially seronegative child was found to have sero‐converted during the period investigated.
Simultaneous presence of herpes simplex and human papilloma virus sequences in human genital tumors
Authors: Di Luca D. , Rorola A. , Pilotti S. , Monini P. , Caselli E. , Rilke F. , Cassai E.
Published: February 2007

Herpes simplex virus (HSV) and human papillomavirus (HPV) sequences were analyzed in tumors of the female lower genital tract, by probing DNA from 13 intraepithelial and 30 invasive neoplastic lesions with radiolabelled HPV‐16 and HPV‐18 DNA as well as cloned fragments of HSV‐2 DNA. Careful removal of stromal tissue from the pathological specimens allowed authentic tumor DNA to be processed. Normal genital tissue obtained from the patients and genital condylomata were included as internal controls. The presence of HPV‐16 or 18 DNA was detected in 12/13 (92.3%) intraepithelial neoplasms and in 16/30 (53.3%) invasive carcinomas. No significant difference was detected in titer or frequency of antibodies to HPV group‐specific antigen in sera from patients and controls. Hybridization to BgIII N fragment of HSV‐2 DNA was detected in 4/13 (30.8%) intraepithelial neoplasms and 4/30 (13.3%) invasive carcinomas but in none of the control tissues. All the 8 samples harboring HSV‐2 homologous sequences were also positive for HPV, supporting the hypothesis of a synergistic association between the 2 viruses. The hybridization analyses performed to study c‐myc involvement in genital oncogenesis did not reveal c‐myc amplification in either invasive or pre‐invasive lesions.
Space‐time clustering and bone tumours: Application of Knox's method to data from a population‐based cancer registry
Authors: Silcocks P. B. S. , Murrells T.
Published: February 2007

The possibility of space‐time clustering in osteosarcoma and Ewing's tumour was studied in a sample of 182 patients aged under 25 years, drawn from a population‐based cancer registry. No evidence of space‐time clustering was found for either disease and this finding supports previous work in this field.
Plasminogen activator production by human tumor cells: Effect on tumor cell‐extracellular matrix interactions
Authors: Varani James , McKeever Paul E. , Fligiel Susanne E. G. , Sttrin Robert G.
Published: February 2007

Cell lines derived from 3 different types of human tumor (e.g., squamous carcinomas, melanomas and gliomas) were examined for production of plasminogen activator activity and for attachment and spreading on various extracellular matrix components in the presence or absence of plasminogen. All of the squamous carcinoma and melanoma lines produced high levels of plasminogen activator activity. In contrast, 4 of 6 glioma lines had undetectable activity. Cells from all 3 tumor types attached and spread on fibrinogen‐coated or fibrin‐coated plastic dishes in the absence of plasminogen. In the presence of exogenous plasminogen, the attachment and spreading of the cells which produced high levels of plasminogen activator activity was inhibited. The plasminogen activator‐deficient cells were much less sensitive to exogenous plasminogen. In the presence of plasminogen, attachment and spreading on fibronectin‐coated dishes was also partially inhibited. In contrast, plasminogen had no effect on the attachment and spreading of the cells on type‐1 or ‐IV collagen, laminin or thrombospondin. Previous studies have shown that tumor‐cell adhesion to the extracellular matrix depends on the synthesis of receptors for extracellular matrix components or on the synthesis of extracellular matrix components themselves. The present study shows that, in addition, the production of enzymes which are capable of degrading these components also influences tumor‐cell adhesion to extracellular matrix moieties.
Contact‐inhibitory factor induces alterations in the distribution and content of specific cytoskeletal elements in an established line of rat hepatic tumor cells
Authors: Higgins Paul J. , Lipkin George , Rosenberg Martin , Ryan Michael P.
Published: February 2007

Established 72/22 rat hepatic epithelial tumor cells, which possess intracellular aggregates of intermediate‐sized filaments resembling Mallory‐body‐like inclusions, were used to assess changes in tumor cell growth and morphology associated with exposure to contact‐inhibitory factor (CIF). CIF reduced 72/22 proliferative rate, increased mean population doubling time by 42%, lowered culture saturation densities to 34–50% of control values and inhibited formation of dense foci. These proliferative changes were due to an apparent prolongation of the G1 phase of the cell cycle during the period of CIF exposure. CIF concomitantly induced a marked increase (by 70%) in cell spreading and loss of both the usual tight (epithelioid) cell juxtaposition and typical ordered colony structure characteristic of untreated populations. However, CIF exposure failed to achieve complete cytoarchitectural “normalization” in 72/22 cells (i.e., dispersal of the Mallory‐body‐like aggregate of intermediate filaments and restoration of a more typical hepatocytic phenotype). Most obvious was a reduction In the integrity of the peripheral band of mlcrofilaments (a structure involved in the maintenance of epithelial cell shape) and a decrease in the content of desmoplakin (a protein component of desmosomal plaques). Changes in these major structural elements appear to be critical events in development of the pleomorphic phenotype and reduced sub‐stratum adhesiveness observed during treatment. CIF‐related fragmentation of peripheral band structures was not reflected in changes in either the total cellular or cytoskeletal‐associated actin contents. The morphologic changes observed under conditions of CIF exposure closely paralleled induced decreases in the cellular content of the actin‐associated membrane skeleton protein p35. These data collectively suggest that CIF may act to alter the composition of the cortical skeleton in cultured liver tumor cells.
The anti‐tumor effect of recombinant interferon alpha or gamma is influenced by tumor location
Authors: Brunda Michael J. , Sulich Viveca , Bellantoni Donna
Published: February 2007

The in vivo anti‐tumor effects of a recombinant human hybrid interferon alpha, rHulFN‐αA/D, and recombinant murine interferon gamma (rMulFN‐γ) were evaluated against experimental hepatic metastases and s.c. tumor growth of the murine reticulum cell sarcoma M5076. The 2 interferons were equally active in preventing experimental hepatic metastases. However, the interferons differed in their relative ability to influence the growth of the same tumor when treatment was initiated following injection of tumor cells. Greater efficacy was obtained in the treatment of metastatic foci in the liver with rHulFN‐αA/D, while rMulFN‐γ was more active in the therapy of an s.c. growing M5076 tumor. These results demonstrate that the same tumor growing at different sites can have different relative sensitivities to IFN‐α and IFN‐γ.
Measurement of plasminogen activator activity from human fibrosarcoma cells by a new microassay
Authors: Rezaee M. , Chen L. , Kramer R. H.
Published: February 2007

Elevated levels of plasminogen activator (PA) activity have been correlated with neoplasia and may have an important role in tumor‐cell invasion and metastasis. We have developed a new caseinolytlc assay that uses an immunochemical approach to measure the activity of PA elaborated by malignant tumor cells. The highly sensitive assay consists in incubating a source of PA (viable tumor cells, cell extracts, or conditioned medium) with purified plasminogen in micro titer plates pre‐coated with a suitable protein substrate such as casein. Clearance of the immobilized protein substrate by PA‐generated plasmin is then measured by a technique based on the enzyme‐linked immunosorbent assay. In experiments using uro‐kinase as a source of PA, the assay displayed near linearity over several log units of urokinase activity and could detect is little as 10−2 Ploug units of PA activity. Besides successfully measuring PA activity produced by the human HT1080 fibro‐sarcoma cell line, the assay permitted detection of significant plasminogen‐independent proteolytic activity generated by intact tumor cells cultured in direct contact with immobilized protein substrates.
The absence of γ‐glutamyltransferase activity in transport‐dependent methotrexate‐resistant hepatoma cells
Authors: Kruger‐McDermott C. , Johnson T. B. , Rej R. , Vanderhoeven T. , Nair M. G. , Galivan J.
Published: February 2007

A cell line derived from H35 hepatoma cells resistant to methotrexate (MTX) as a result of a defective transport system for MTX has been examined to determine how closely the variant resembles the parent cells with regard to other biochemical properties. The capacity of extracts of resistant cells to catalyze the poly‐γ‐glutamylation of MTX was approximately twice as great as that of wild‐type cell extracts. Evidence of similarity between wild‐type and H35 R0.3 cells was derived from the equitoxic activity to both cell lines of non‐classical antifolates and other miscellaneous antineoplastics which act by a variety of mechanisms. Two phenotypic markers of hepatic cell function, α‐aminoisobutyric acid (AIB) transport and tyrosine aminotransferase (TAT) activity inducibility, were present in both cell types, demonstrating the maintenance of these phenotypic properties in the H35 R0.3 cells. γ‐Glutamyltransferase (GGT, EC 2.3.2.2) activity differed in that it was present in wild‐type cells and barely detectable in H35 R0.3 cells. The GGT activity reappeared in the H35 cells when they regained MTX sensitivity after incubation for 14–20 weeks in MTX‐free media. Although defective MTX transport appeared to be correlated with the disappearance of GGT activity in an H35 variant cell line, no functional relationship between them is apparent at this time. It is possible that a lack of GGT activity may be evidence of a more differentiated phenotype in the transport‐resistant cell line.
Effects of retinoids and interferon‐gamma on cultured breast cancer cells in comparison with tumor necrosis factor alpha
Authors: Marth Ch. , Zech J. , Böck G. , Mayer I. , Daxenbichler G.
Published: February 2007

The combination of retinoic acid or tumor necrosis factor alpha (TNF‐alpha) with interferon gamma (IFN‐gamma) resulted in a synergistic amplification of the anti‐proliferative effect of IFN‐gamma on cultured breast cancer cells. Retinoic acid could be replaced by other biologically active retinoids. This synergism was also observed for the induction of 2′‐5′‐oligoac enylate‐synthetase, an enzyme which is not expressed constltutively on BT‐20 human breast cancer cells and not inductile by retinoic acid or TNF‐alpha alone. However, both substances augmented the IFN‐gamma‐mediated expression. On the other hand, only TNF‐alpha and not retinoic acid was able to increase the IFN‐gamma induced expression of HLA‐DR on the cell surface. Both cytokines antagonized the IFN‐gamma effect on detachability of cultured BT‐20 cells. The combinations of retinoic acid with IFN‐gamma increased the down‐regulation of specific binding sites for 125 l‐IFN‐gamma. On the other hand, IFN‐gamma exerted no effect on the cancer traction of the cytoplasmic binding protein for retinoic acid. Data obtained in this study demonstrate a different patten of action between retinoic acid and TNF‐alpha regarding their synergism in combination with IFN‐gamma.
Influence of docosahexaenoic acid in vitro on intracellular adriamycin concentration in lymphocytes and human adriamycin‐sensitive and ‐resistant small‐cell lung cancer cell lines, and on cytotoxicity in the tumor cell lines
Authors: Zulstra J. G. , De Vries E. G. E. , Muskiet F. A. J. , Martini L. A. , Timmer‐Bosscha H. , Mulder N. H.
Published: February 2007

An increase in the therapeutic effects of cancer chemother‐apeutic agents and circumvention of drug resistance in cancer cells might result from an increase in the intracellular drug lave. Alteration of the lipid domain of the cell membrane can result in a higher intracellular drug level. This alteration was achieved in human lymphocytes and in human adriamycin (ADR)‐sensitive and ‐resistant small‐cell lung carcinoma cells in vitro by incubation with docosahexaenoic acid (22:6). Incorporation of the fatty acid in cellular phospholipids was measured by gas chromatographic analysis. A significant increase of 22:6 could be reached without loss of viability in all 3 cell types. Incorporation was demonstrated notably in the phos‐phalidyl choline, phosphatidyl ethanolamine and phosphati‐dylserine, and was most pronounced in the phosphatidyl cholne of the ADR‐resistant line. After a 1‐hr incubation with ADR, a 10–30% increase in intracellular adriamycin concentration was found in all 3 cell types previously incubated for 4 days with 22:6. After 1 hr incubation with ADR there was no increase in cytotoxicity in the sensitive cell line when measured by soft agar clonogenic assay and a partial reversal (52 to 14) of resistance factor (ratio of drug doses to produce 50% growth inhibition) in the resistant cell line. Increasing the time of ADR exposure from 1 to 4 hr further reduced the resistance factc r to 8.6.
Characterization of a new human papillomavirus (HPV 41) from disseminated warts and detection of its DNA in some skin carcinomas
Authors: Grimmel M. , De Villiers E.‐M. , Neumann Ch. , Pawlita M. , zur Hausen H.
Published: February 2007

A new human papilla ma virus type (HPV 41), distantly related to known HPV prototypes, was isolated from a patient with disseminated facial, peri‐anal and foot warts (epidermodysplasia verruciformis was not diagnosed). The viral DNA was molecularly cloned in 2 BamHI restriction fragments with sizes of 6.5 kb and 0.98 kb, respectively. The classification of this cloned DNA as a new type is based on the degree of cross‐hybridization with 40 HPV types under conditions of varying stringency. A total of 106 benign and malignant skin lesions, as well as 71 malignant tumours of different origins, were screened for the presence of HPV‐related sequences. In 2 out of 10 squamous‐cell carcinomas and in I of 3 arsenic keratoses HPV 41 DNA sequences could be detected.
The significance of new abnormal isoenzymes of 5′‐nucleotide phosphodiesterase in the diagnosis of human liver cancer
Authors: Lin Ke‐Min , Ye Si‐Yuan , Liu Qi‐Fu
Published: February 2007

In 1986, we reported that abnormal 5′‐nudeotide phosphodiesterase (5′‐NP) (oligonucleate: 5′‐nucleotidohydrolase, EC 3.1.4.1) isoenzymes (5′‐NP 1 and 5′‐NP V + VI) were observed in the serum of patients with liver cancer. The results of the present study show that the 5′‐NP 1 positivity rate is 99.2% (234/236), specificity 74.9%; and the 5′‐NP V + VI posittvity rate is 77.5% (183/236), specificity 95.3% in liver cancer. 5′‐NP 1 positivity rate is 86.7% (13/15) and 5′‐NP V + VI positivity rate is 46.7% (7/15) in metastatic liver cancer. These 3 abnormal isoenzyme bands were all present in the serum of 6 patients with liver cancer before radical resection and disappeared after successful resection, but they were all present in the serum of 6 other liver cancer patients before and after palliative operation. In 2 cases of small liver cancer (diameter less than 4cm), 5′‐NP I and 5‐NP V + VI were strongly positive. It may be considered that the new 5′‐NP abnormal isoenzyme bands are specific markers and will be useful for diagnosis of human liver cancer.
An immunohistochemical study of laminin, type‐IV collagen and type‐III pN‐collagen with relation to reticular fibres in Hodgkin's disease
Authors: Karttunen Tuomo , Alavaikko Martti , Apaja‐Sarkkinen Meeri , Autio‐Harmainen Helena
Published: February 2007

The distribution of aminoterminal propeptide of type‐III procollagen (indicating the presence of type‐III pN‐collagen, i.e., type‐III collagen molecule with a non‐cleaved aminoterminal propeptide}, laminin and type‐IV collagen was studied by immunohistochemical methods. The results were compared with the distribution of reticular fibres using Gomori's reticulin stain. Lymph nodes from 20 cases of Hodgkin's disease (HD) and 3 spleens affected by nodular sclerosis HD were studied. The reticular fibres stained for all the antigens investigated, the strongest reaction being for pN type‐III collagen. Thick fibres stained mainly for type‐III pN‐collagen, the BM proteins being located in a fragmented rim on the surface. The distribution and composition of fibres was similar in both, nodal and extranodal infiltrations. The morphological alterations noted in the fibres comprised (1) compression between nodules in the nodular type of lymphocyte‐predominant HD, and (2) fragmentation, present in collections of histiocytes in lymphocyte‐predominant HD. BM proteins and type‐III pN‐collagen were present in the walls of the sinuses and vessels. The marginal sinuses were often partially spared in spite of extracapsular invasion. Our results suggest that laminin, type‐IV collagen and type‐III pN‐collagen are important components of reticular fibres in HD and that the composition of the, fibres is similar to that seen in the normal lymph node.
Mouse tumor‐associated macrophages do not generate procoagulant activity in response to different stimuli
Authors: Erroi A. , Casali B. , Donati M. B. , Mantovani A. , Semeraro N.
Published: February 2007

Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of human and experimental tumors, might contribute to fibrin deposition within malignant tissues through the production of procoagulant activity (PCA). We have studied the PCA of tumor‐associated macrophages (TAM) in 2 poorly immunogenic, metastatic murine sarcomas (mFS6 and MN/MCAI); peritoneal macrophages (PM) from tumor‐bearing and control animals were also studied, as reference cell populations. PCA was evaluated by a one‐stage clotting assay immediately after isolation (basal PCA) and following in vitro stimulation. Basal PCA was very low (< 1 U/104 macrophages) in all cell preparations. Exposure of PM from both normal and tumor‐bearing animals to bacterial endotoxin (lipopolysaccharide, LPS), phorbol myristate acetate (PMA) or the chemotactic peptide formyl‐methionyl‐leucyl‐phenylalanine (FMLP) resulted in 10‐, 7‐ and 3‐fold increases in PCA, respectively. In contrast, TAM from mFS6 and MN/MCAI consistently fatted to generate PCA in response to different concentrations of the same stimuli. Treatment of TAM with aspirin did not affect cell unresponsiveness. Fluorescence microscopy showed that almost all PM were stained with fluorescein isothiocyanate (FITC)‐LPS, while < 10% of the TAM were stained. These data, coupled with previous evidence that TAM have a lower number of specific binding sites for phorbol esters than PM, suggest that the defective responsiveness of TAM to endotoxin, PMA and, possibly, FMLP, is due to the lack, or very tow expression, of binding sites for these agents on the cell surface. The tumor environment may orient the functional status of in situ macrophages in a direction less favorable to the host.
Reducing effects of rodent malaria on hepatic carcinogenesis induced by dietary aflatoxin B1
Authors: Angsubhakorn Subhkij , Bhamarapravati Natth , Sahaphong Somphong , Sathiropas Permsin
Published: February 2007

The present study was undertaken to evaluate the effects of Plasmodium berghei infection on the development of liver tumors induced in male Buffalo rats by aflatoxin B1 (AFBF). Intraperitoneal (i‐p.) injection of 106 parasitized red blood cells (pRBC) into the rat 12 days prior to administration of 2 ppm dietary AFB1 for 10 weeks diminished hepatocellular carcinoma (HCC) induction compared to that observed in rats given AFB1 alone at weeks 60–82. No animals in a control group developed HCC lesions, while only 1 of 22 rats treated With P. berghei alone developed a neoplastic nodule at week 82. These data suggest a reducing effect of P. berghei on the development of liver tumors induced by AFB1 in male Buffalo rats.
Metastasis of a human melanoma cell line in the nude mouse
Authors: Wilson E. Lynette , Gartner Maria F. R. M. , Campbell J. A. H. , Dowdle Eugene B.
Published: February 2007

A human melanoma cell tine has been established which when inoculated subcutaneously into nude mice, is consistently metastatic. In order to document blood‐borne spread, it was necessary to excise the primary tumour so prolonging the life of the animal and allowing metastases to become apparent. Macroscopicatly detectable metastatic spread at autopsy was reliably indicated by weight loss of the animals. Metastases were widespread and involved the lungs, abdominal cavity and organs and the gonads. The size of the primary tumour at the time of its removal, and nat the period of s.c. growth, determined the incidence of metastatic disease. Removal of tumours weighing less than 0.6 g prevented metastasis, whereas all of the animals showed widely disseminated disease if the tumour was allowed to attain a size of 1.6 g before excision.
Role of different normal hematopoietic regulatory proteins in the differentiation of myeloid leukemic cells
Authors: Lotem Joseph , Shabo Yosef , Sachs Leo
Published: February 2007

There are 4 different normal myeloid hematopoietic cell growth‐inducing proteins MGI‐I (CSF or IL‐3) that induce normal precursor cells to multiply and form clones containing only macrophages (MGI‐IM = M‐CSF = CSF‐I), only granu‐locytes (MGI‐IG = G‐CSF), both granulocytes and macrophages (MGI‐IGM = GM‐CSF), or granulocytes, macrophages, eosinophils, mast cells, megakaryocytes and erythroid cells (interleukin‐3) (IL‐3). There is another type of normal myeloid regulatory protein (MGI‐2) with no MGI‐I (CSF or IL‐3) activity which can induce differentiation of normal myeloid precursors and certain clones of myeloid leukemic cells. The present results with MGI‐2 and pure recombinant MGI‐IG, MGI‐IGM and IL‐3 have shown that different clones of myeloid leukemic cells can be induced to differentiate by different hematopoietic regulatory proteins. One type of leukemic clone is induced to differentiate to mature cells only by MGI‐2 and is partially differentiated by MGI‐IG, a second type is differentiated only by MGI‐IGM or IL‐3, and other workers have found a third type that is differentiated only by MGI‐IG. The presence of surface receptors does nat necessarily make leukemic cells differentiation competent for these hematopoietic regulatory proteins. All 4 types of MGI‐I (CSF or IL‐3) induce endogenous synthesis of MGI‐2 in normal myeloid precursor ceils. It is suggested that, in addition to their potential therapeutic effect on the development of normal hematopoietic cells, MGI‐2, MGI‐IG, MGI‐IGM and IL‐3 all have the potential for differentiation‐directed therapy of leukemia in leukemic cells that can be differentiated by one of these normal hematopoietic regulatory proteins.
Isolation of simian immunodeficiency virus from african green monkeys and seroepidemiologic survey of the virus in various non‐human primates
Authors: Ohta Yoshihiro , Masuda Takao , Tsujimoto Hajime , Ishikawa Koh‐Ichi , Kodama Toshiaki , Morikawa Shigeru , Nakai Masuyo , Honjo Shigeo , Hayami Masanori
Published: February 2007

Sixteen isolates of simian retrovirus closely related to human immunodeficiency virus (HIV) were obtained from healthy African green monkeys (AGM) (Cercopithecus aethiops). The first isolate was obtained from a monkey seropositive for HIV, and the others were isolated from monkeys harboring antibodies to the first isolate. These simian retro‐viruses were referred to as simian immunodeficiency virus from AGM, SIV[AGM], due to their cross‐reactivities with HIV structural proteins. These SIV[AGM] isolates were found by Western blotting analysis to have virus‐specific proteins of 120, 66, 55, 32–40, 24 and 17 kDa, which were all similar in size to the analogous proteins of HIV. Putative gas proteins of p55, p24 and pl7 were recognized by sera of human AIDS patients, but the corresponding env proteins of 32–40 and 120 kDa showed only weak cross‐reactivity with those of HIV. The transmembrane glycoproteins of these 3 SIV[AGM] isolates showed size heterogeneity, being 32, 35 and 40 kDa. This virus had particles that were morphologically similar to those of HIV, and had Mg2+ ‐dependent reverse transcriptase. Furthermore, the SIV[AGM] showed tropism and cytopathic effects on CD4‐positive human cell tines. In a sero‐epidemiological survey of SIV[AGM] in various non‐human primates, 2 other African monkey species, the mandrill and de Brazza's monkey, were also found to have antibodies to SIV[AGM]. These HIV‐related simian retroviruses will be important in determining the origin and transmission of HIV group viruses, and may provide useful animal models for studies on the infection and pathogenesis of HIV and AIDS.
Interferon treatment markedly inhibits the development of tumor metastases in the liver and spleen and increases survival time of mice after intravenous inoculation of friend erythroleukemia cells
Authors: Gresser Ion , Maury Chantal , Woodrow David , Moss Jill , Grütter Marcus G. , Vicnaux Françoise , Belardelli Filippo , Maunoury Marie‐Thérèse
Published: February 2007

To investigate the effect of interferon treatment on the development of tumor metastases, DBA/2 mice were injected i.v. with 2 × 106 Friend erythroleukemia cells (FLC) (equivalent to about 5 × 105 LD50). FLC multiplied rapidly in the liver and spleen and all untreated or control treated mice died between 7 and 12 days. Daily treatment of mice with potent preparations of mouse interferon α/β was initiated 3 to 72 he after i.v. inoculation of tumor cells, at times when FLC were already present in the liver and spleen. Interferon treatment resulted in a 100 to 1,000‐fold inhibition of the multiplication of FLC in the liver and spleen and a marked increase in mean survival time. Small numbers of tumor cells persisted in the liver and spleen in some interferon‐treated mice and could be recovered by bioassay several weeks after tumor inoculation‐Most interferon‐treated mice died with tumor in the ensuing months. Three of 34 Interferon‐treated mice were considered cured as they were alive at 386, 325 and 284 days after tumor inoculation. Daily treatment of tumor‐inoculated mice with human recotnbinant interferons αD and αBDDD, which had antiviral activity on mouse cells in culture, also increased the survival time of mice injected i.v. with FLC. The use of the interferon‐resistant 3C 18 line of FLC suggests that the marked inhibition of development of established liver and spleen metastases was not due to a direct effect of Interferon on the tumor cells, but was host‐mediated.
Distribution and survival of passively transferred lymphoblasts in normal and tumor‐bearing mice
Authors: Normann S. J. , Cornelius J.
Published: February 2007

Although most circulating lymphocytes are long‐lived small lymphocytes, it is the recently‐divided medium and large‐sized lymphoblasts that most clearly migrate to sites of inflammation, and they do so without regard to immunologic commitment. The tumor‐bearing state frequently suppresses macrophage accumulation at inflammatory sites but it is not known whether lymphocyte traffic is similarly affected. We addressed this issue using passively transferred radiolabelled lymphoblasts. Lymphoblasts readily entered s.c. fibrosarcomas transplanted to C57BL/6 mice. Large and small tumors acquired the same number of lymphoblasts per gram of tumor, indicating the absence of an anti‐inflammatory reaction. However, the intra‐tumoral survival of lymphoblasts was shorter in large than in small tumors. Shortened survival was noted also in spleen and whole body of animals bearing tumors. Shortened survival rather than impaired emigration may contribute to the increase in turn or lymphocyte ratio observed with large tumors. The adverse effect of tumor bearing on lymphoblast survival may be limited to tumors which acquire a high percentage of passively transferred lymphocytes since intraperitoneal P‐815 maitocytomas in DBA/2 mice acquired few labelled lymphoblasts and did not alter lymphoblast survival. These results are important for host resistance to tumor growth and therapeutically for the use of lymphocyte cytotoxic cells induced to proliferate in vitro.
Refining the prognostic significance of dna ploidy status in colorectal cancer: A prospective flow cytometric study
Authors: Jones D. J. , Moore M. , Schofield P. F.
Published: February 2007

A consecutive series of 123 colorectal cancers, prospectively followed for 3 years, was studied to determine if the prognostic significance of DNA ploidy related to: (a) thresholds used to define DNA aneuploidy, or (b) aneuploid sub‐groups defined by DNA index (DI) and peak size. Aneuploidy was defined using 3 methods depending on the minimum proportion of nuclei considered to constitute an aneuploid peak; type 1, 5%; type 2, 10%; type 3, 10% if Dl is 1.1–1.8, but 15% if Dl is 1.9–2.1. DNA aneuploidy rates were type 1, 75%; type 2, 67%; type 3, 58%. The significance of clinical and pathological correlations varied with the use of different methods. All were associated with a significant DNA diploid survival advantage which was strongest for type 3 (p=0.006). Dl was unrelated to survival irrespective of the presence or absence of an associated S/G2; 33% with a Di of 1.1–1.8 and 35% with a Dl of 1.9–2.1 survived. Prognosis was inversely proportional to aneuploid peak size, 48% with small peaks (<20%), 30% with intermediate peaks (>20%<40%), but none with large peaks (>40%) survived (p=0.03). We conclude that: (a) thresholds used to define DNA aneuploidy affect the prognostic significance of DNA ploidy; (b) survival is independent of the Dl of aneuploid peaks; and (c) measurement of aneuploid peak size refines the prognostic value of DNA ploidy.
Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma
Authors: Yasui Wataru , Hata Jotaro , Yokozaki Hiroshi , Nakatani Hiroshi , Ochiai Atsushi , Ito Hisao , Tahara Eiichi
Published: February 2007

The expressions of epidermal growth factor (EGF) and its receptor were studied immunohistochemically in a total of 156 gastric carcinomas; 26 early and 130 advanced. No EGF immunoreactivity was found in early carcinomas, while EGF‐positive tumor cells were detected in 38 (29.2%) of the 130 advanced carcinomas. EGF receptor immunoreactivity was detected in one (3.8%) of the 26 early carcinomas and in 44 (33.8%) of the 130 advanced carcinomas, the incidence being significantly different (p<0.01). Out of the 130 advanced carcinomas, 17 (13.1%) had synchronous expression of EGF and its receptor and most of the tumors with strong expression of EGF were positive to EGF receptor. A significant correlation was observed between the depth of tumor invasion and EGF or its receptor immunoreactivity in tumor cells (p<0.05). Furthermore, a good correlation was demonstrated between the synchronous expression of EGF and its receptor and the depth of tumor invasion or the tumor staging. The incidence of cases with EGF in metastatic tumors was significantly higher than that in primary tumors (p<0.05). Patients with synchronous expression of EGF and its receptor had a far poorer prognosis than those without EGF and receptor.