bluuebunny/crossref_metadata_2025 huggingface dataset:
Alteration of the extracellular matrix of cultured human keratinocytes by transformation and during differentiation
Authors: Brown Keith W. , Parkinson E. Kenneth
Published: February 2007

We have investigated the production of 3 extracellular matrix proteins (fibronectin, laminin and entactin) and glycosaminoglycans (GAGs) by keratinocytes derived from human squamous‐cell carcinomas (SCCs). All the SCC lines retained the ability to synthesize fibronectin, laminin and entactin, and to incorporate them into an extracellular matrix. In some of the SCC lines fibronectin production was higher than in normal keratinocytes, and in most lines laminin production was equal to or higher than that seen in normal keratinocyte strains. All the tumorigenic SCC lines produced less entactin than normal keratinocytes. Five out of 7 SCC lines showed a shift in GAG production compared with normal keratinocytes, so that in these lines heparan sulphate was the major GAG as opposed to hyaluronic acid in the normal keratinocytes. As these changes could have been a consequence of the reduced differentiation found in the SCC lines, we fractionated normal keratinocytes into 4 size classes corresponding to different stages of differentiation, using Percoll gradient centrifugation. It was found that the ability to produce these extracellular matrix glycoproteins and GAGs was lost as keratinocytes terminally differentiated. However, this did not explain the matrix changes seen in the SCC lines, since the undifferentiated normal keratinocytes produced a normal pattern of extracellular matrix components. Nonetheless, the loss of extracellular matrix production may well explain the reduction in substratum adhesiveness which occurs as keratinocytes terminally differentiate.
Down‐regulation of peripheral blood cell interferon receptors in chronic myelogenous leukemia patients undergoing human interferon (HuIFNα) therapy
Authors: Maxwell Beth Lynn , Talpaz Moshe , Gutterman Jordan U.
Published: February 2007

Our interest in studying interferon (IFN) receptor activity in peripheral blood cells (PBCs) from patients with chronic myelogenous leukemia (CML) receiving therapeutic doses of partially purified leukocyte IFN (IFNα) stems from a need for more adequate monitoring of IFN therapy. The binding of 35S‐labelled recombinant DNA‐derived leukocyte clone A IFN (35SrlFNαA) to PBCs from 8 patients with CML was determined before and during IFNα treatment. The patients′ mean pretherapy binding level (0.049 femtomoles of bound 35S‐rlFNαA) was in the range of values obtained from 4 normal donors (mean of 0.054 femtomoles bound). Within 24 hr of the first IFNα dose, the mean femtomoles bound decreased 10‐fold and remained low during the course of IFNα treatment. In I/I patient, we demonstrated that this decreased binding was due to a loss in number of IFN receptors. The apparent number of receptors after 5 doses of IFNα decreased from approximately 600 receptors per cell at pretherapy to approximately 75 receptors per cell, with no difference in the dissociation constants (1.13 × 10−10M, 0.968 × 10−10M, before and during treatment, respectively). In 4/4 patients, we demonstrated indirectly that the decreased binding was not due to receptor saturation as a result of residual circulating IFNα. In 3/3 patients, we demonstrated a gradual recovery of binding capacity after incubating the patients′ PBCs at 37°C. Within 2–7 days in vivo recovery of binding, comparable to pretherapy levels, was observed in 3/3 patients whose IFNα therapy was discontinued. Combining all these data, we conclude that in both responding and nonresponding patients with CML, IFNα exposure induces decreased binding of labelled IFN when a single recombinant DNA‐derived IFN species is used. We feel the supporting data indicate that the decreased binding capacity may be due to receptor down‐regulation. In the limited number of patients studied thus far, there was no correlation between clinical hematologic response and occurrence of down‐regulation, however, down‐regulation of cell surface receptors may be required to sustain a biological effect. Further studies of both the kinetics of down‐regulation and activation of key enzyme systems are required to fully evaluate the relevance of these findings.
Phenotypic dynamics of tumor progression in human malignant melanoma
Authors: Bröcker Eva‐Bettina , Suter Ludwig , Brüggen Josef , Ruiter Dirk J. , Macher Egon , Sorg Clemens
Published: February 2007

The phenotypic changes in human melanoma cells during the course of tumor progression were studied with monoclonal antibodies (MAbs) against the melanoma‐associated antigens (MAA) M.2.2.4, H.2.8.10, K.1.2, A.1.43, and A.10.33, and HLA‐(A.B.C and D). Cryostat sections of 172 primary melanomas of the skin, 157 melanoma metastases and 56 nevi were investigated with an indirect immunoperoxidase method. Phenotypic heterogeneity was observed within lesions at all stages, and also within different tumors of the same patients. Despite this heterogeneity, principles of antigen expression were found. From the reaction pattern of MAbs, the following classifications of antigens were derived: “constitutive” markers of nevomelanocytic cells (M.2.2.4 and H.2.8.10) were found expressed over a wide range of local and systemic tumors. One MAA. K.I.2 (Suter et al., 1985), hat declines with progression of melanoma, was classified as an “early” antigen, whereas MAA that appear in primary melanoma in proportion to invasiveness, and which are expressed in metastases of lymph nodes and visceral organs (A.I.43, and A.10.33), were classified as „late”︁ markers of tumor progression. HLA‐antigens were classified as „intermediate”︁ markers, HLA‐A,B,C, as an „early‐intermediate”︁, and HLA‐DR as a „late‐intermediate”︁ marker. The occurrence of class II HLA, A.I.43‐, and A.10.33‐positive tumor cells in primary melanoma indicates a high metastatic potential of tumors, independent of tumor thickness. The data show that local and systemic progression of melanoma is associated with qualitative changes in tumor cells which can be recognized by MAbs.
Serum micronutrient levels in relation to gastric pathology
Authors: Haenszel William , Correa Pelayo , López Alfredo , Cuello Carlos , Zarama Guillermo , Zavala Diego , Fontham Elizabeth
Published: February 2007

As part of an ongoing cohort study of gastric cancer precursors in Narino, Colombia, blood levels of ascorbic acid, vitamin E, retinol, pre‐albumin, retinol binding protein and carotenoids were measured and correlated with histopathologic findings of gastric biopsies. Carotene levels in both sexes and vitamin E levels in males were significantly lower in subjects with gastric dysplasia than in subjects with normal mucosa and subjects with less advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia). No other significant correlations were found.
Case control study of cervical cancer in Herrera Province, Republic of Panama
Authors: Reeves William C. , Brinton Louise A. , Brenes Maria M. , Quiroz Evelia , Rawls William M. , De Britton Rosa C.
Published: February 2007

A previous survey found the average annual age‐adjusted incidence of cervical cancer in Herrera Province, Panama, to be 79/100, 000, exceeding any other reported world rate. In an effort to clarify the reasons for this excessive occurrence, a case‐control study was conducted among patients diagnosed between 1974‐1980. Sixty‐six percent of cervical cancer patients from Herrera Province were alive and were contacted by the study team; of these 91% were successfully interviewed and provided serum specimens. The total study encompassed 156/169 surviving patients and 309 age‐neighborhood matched controls. Sexual promiscuity was uncommon, but it exerted a major effect, with those reporting 4 or more life‐time sex partners being at a 4‐fold excess risk compared to those reporting only one partner. First intercourse at a young age was common (21% began sexual activity prior to age 16) but it failed to alter risk once number of partners was taken into account. Oral contraceptive use was associated with a 2‐fold excess risk and this was not substantially affected by controlling for sexual parameters. Thirty‐three percent of the study subjects had anti‐herpes‐simplex type‐2 antibody as measured by both neutralization and radioimmunoassays. Although results of the neutralization test were not predictive of risk, women with a radioimmunoassay indicative of HSV‐2 infection were at a 40% excess risk for cervical cancer after adjustment for sexual characteristics.
Multipotentiality of yolk‐sac carcinoma cell clones
Authors: Van Hove L. , Sobis H. , Lu Y. L. , Vandeputte M.
Published: February 2007

Yolk‐sac carcinoma (YSCa) clones were isolated by manual cloning under visual control. By morphology, immunohistology and histochemistry the clones were shown to differentiate in vitro into visceral and parietal yolk‐sac cells and in vivo into visceral and parietal yolk‐sac cells, trophoblast and mesenchyme. Trophoblast and mesenchyme were only recorded in rat YSCa derived from displaced yolk sac but not in embryoderived YSCA. Hence YSCa cells displaying a visceral and parietal yolk‐sac pattern as well as the trophoblastic and the mesenchymal structures should have a common cell ancestor.
Characterization of human tumor necrosis factor produced by peripheral blood monocytes and its separation from lymphotoxin
Authors: Kelker Hanna Chroboczek , Oppenheim Joel D. , Stone‐Wolff Donna , Henriksen‐DeStefano Dorothy , Aggarwal Bharat B. , Stevenson Henry C. , Vilček Jan
Published: February 2007

Cultures of human peripheral blood leukocytes (PBL) induced with phytohemagglutinin (PHA) and the phorbol ester 12‐0‐tetradecanoylphorbol 13‐acetate (TPA) produced two types of cytotoxic proteins, indistinguishable in the in vitro assay employing murine L 929 cells as targets. One of these proteins had the antigenic and physicochemical properties of lymphotoxin (LT). We have identified the other cytotoxin as tumor necrosis factor (TNF), mainly on the basis of antigenic cross‐reactivity demonstrated with antiserum to TNF, and also by its characteristic physicochemical properties and cell source. Unlike LT, PBL‐derived TNF did not bind to Concanavalin A‐Sepharose or to several other agglutinin‐Sepharose columns specific for carbohydrate moieties common in glycoproteins. The molecular weight of native TNF determined by gel filtration was approximately 40,000 while SDS‐PAGE revealed a single sharp peak of 16,500 ± 500. When cultures of monocytes and lymphocytes separated by elutriation were stimulated with PHA and/or TPA, monocytes were the major source of TNF. In contrast, only lymphocytes produced LT. A mixture of antisera to TNF and LT neutralized all cytotoxicity of crude human lymphokine preparations for L 929 cells, suggesting that TNF and LT are either the only, or the major, cytotoxic proteins present in such crude lymphokine preparations demonstrable in this assay.
Selective dna‐amplification induced by carcinogens (initiators): Evidence for a role of proteases and DNA polymerase alpha
Authors: Heilbronn Regine , Schlehofer Jörg R. , Yalklnoglu A. Oüzkan , Hausen Harald Zur
Published: February 2007

Inhibitors of DNA polymerase alpha (aphidicolin, phosphonoacetic acid, phosphonoformic acid) efficiently inhibit initiator‐induced amplification of SV40 DNA sequences in the SV40‐transformed Chinese hamster cell line C0631. Amplification is also inhibited by various protease inhibitors (antipain, leupeptin, aprotinin, alpha‐I‐antitrypsin, epsilon‐amino‐caproic acid, soy‐bean protease inhibitor), by the non‐initiating but DNA‐damaging agent caffeine, and by sodium butyrate, which inhibits DNA synthesis by histone modification. In contrast, an inhibitor of topoisomerase II, nalidixic acid, enhances amplification when applied simultaneously with initiating treatment. This latter compound does not induce amplification when applied without initiator. Cycloheximide induces DNA amplification in the same way as chemical and physical carcinogens. This amplification can still be observed when protein synthesis is completely blocked. The data suggest a complex mechanism of selective DNA amplification. The possible involvement of proteases leading to a functional modification of DNA polymerase alpha is discussed.
Biological effects of γ‐interferon on human tumor cells: Quantity and affinity of cell membrane receptors for γ‐IFN in relation to growth inhibition and induction of HLA‐DR expression
Authors: Ücer Ugur , Bartsch Helge , Scheurich Peter , Pfizenmaier Klaus
Published: February 2007

A large difference in the number of γ‐IFN receptors was found on a variety of human tumor cell lines with a range of 0.4 to 15 × 103 binding sites/cell. The receptor number did not correlate with the potential responsiveness of the cells to γ‐IFN, in regard to either growth inhibition or induction of HLA‐DR expression, two independently regulated γ‐IFN effects. However, with respect to HLA‐DR expression it was found that the γ‐IFN sensitivity of inducible cell lines depended on the number of receptors, so that with increasing number of receptors present on these cells lower doses of γ‐IFN were required for induction of the γ‐IFN effect.
Lysis of type‐i collagen by squamous carcinomas of the head and neck
Authors: Burman J. F. , Carter R. L.
Published: February 2007

Lysis of type‐1 collagen by squamous carcinomas of the head and neck has beeen studied in freshly excised tissues, xenografts and established cell lines. Investigations with 35 freshly excised tumours showed only low levels of active and total collagenase in both carcinomas and controls. A difference became apparent when the tissues were set up in explant organ culture where a significant (P < 0.05) increase in total collagenase was found in 13/19 tumours compared with paired control tissues over a 4–week culture period. Two xenografts showed little capacity to lyse collagen in vitro and there was only limited evidence of an increase in total collagenase after explantation and growth in organ culture. Twenty tumour cell lines showed low levels of active collagenase. Total collagenase levels were significantly increased (p < 0.05) in 4 of the the cell lines derived from cancers of the tongue; this activity was sustained in subsequent passages. Six control fibroblastoid cell lines also showed low levels of active collagenase. Levels of total collagenase were consistently high, but this activity was transient and declined in subsequent passages. Co‐cultivation experiments with 11 tumour‐cell lines and 5 fibroblastoid cell lines showed some enhanced, synergistic destruction of collagen. Parallel experiments with supernatant media from the carcinoma and fibroblastoid lines showed no enhancement, indicating that intact carcinoma cells and fibroblastoid cells are requited for synergistic collagenolysis to take place.
In vitro and In vivo antitumor activity of lymphokine‐induced cytotoxic cells
Authors: Ting Chou‐Chik , Wunderlich John R. , Hargrove Myrthel E. , Winkler David
Published: February 2007

The present study demonstrates that LICC possess both in vitro and in vivo antitumor activity. The LICC were generated by culturing normal spleen cells with syngeneic peritoneal cells and indomethacin, or with a conditioned medium containing IL 2 with or without a putative new lymphokine, the CCDF. The LICC thus generated selectively killed the lymphoid or solid tumor targets of different H‐2 haplotypes and of different etiological origins. The precursors of LICC were probably NK‐like cells. The effectors were neither classical NK nor classical cytotoxic T lymphocytes. The LICC were very effective in preventing growth of both lymphoid and solid tumors in vivo, and Thy I+ cells were essential for the anti‐tumor effect. The ability to generate LICC was preserved in the tumorbearing hosts until the terminal stage of tumor growth, when the generation of suppressor T‐cells interfered with LICC induction. LICC seem to play an important role in defense against non‐immunogenic tumors.
Gastrointestinal carcinoma‐associated antigen detected by a monoclonal antibody in dysplasia and adenocarcinoma associated with chronic ulcerative colitis
Authors: Olding Lars B. , Åhren Christer , Svalander Christian , Thurin Jan , Karlsson Karl‐Anders , Koprowski Hilary
Published: February 2007

Colorectal tissue specimens from 13 patients with chronic ulcerative colitis, of whom all had epithellal dysplasia and 2 had adenocarcinoma, were tested for the presence of gastrointestinal carcinoma‐associated antigen (GICA), using an immunoperoxidase technique with a monoclonal antibody (MAb) against this antigen. GICA was present in the formaldehyde‐fixed and paraffin‐embedded sections of dysplastic and cancer tissue but absent from normal or hyperplastic epithelium. However, the pattern and extent of staining with the antibody did not correlate with the degree of dysplasia, i.e., ‘mild’ dysplasia was often positive, and ‘severe’ dysplasia was sometimes negative. Changes classified as ‘indefinite for dysplasia but probably negative’ were variable in their expression of GICA. The adenocarcinomas were selectively labelled within cell clusters. In contrast, ulcerative colitis (UC) patients with severe inflammatory changes but with no detectable dysplasia were negative for GICA. GICA could be eluted from paraffin blocks of dysplastic tissue and biochemically characterized as a glycolipid. The detection of this antigen might be a useful complement to morphological examination in discriminating between precancerous and benign epithelial lesions of the colon.
SQM1 Antiody defines a surface membrane antigen in squamous carcinoma of the head and neck
Authors: Boeheim Klaus , Speak Jonathan A. , Frei Emil , Bernall Samuel D.
Published: February 2007

We produced murine monoclonal antibodies (MAbs) directed against the surface membrane of squamous‐cell carcinoma of the head and neck (SCCHN). One antibody, SQMI, was determined by immunofluorescence and radioimmunoassay to be reactive with 13/13 SCCHN cell lines derived from different sites of the head and neck area. No binding reaction was observed with normal fibroblasts, red blood cells, nucleated bone‐marrow cells or epithelial cells from normal oral mucosa. SQMI reactivity was observed with primary cultures of normal epidermal and bronchial epithelial cells. Significant reactivity was found with 2/4 cell lines derived from small‐cell carcinoma of the lung but little or no reactivity was found with other lung cancer cell lines. Various cell lines derived from other cancers including breast, colon, and ovarian carcinomas, melanoma, neuroblastoma and leukemia were generally unreactive. Seventeen out of 18 fresh frozen specimens of SCCHN were strongly reactive with SQMI antibody. However, autopsy specimens from the heart, liver, kidney, spleen, colon, subcutaneous fat and skin connective tissue were unreactive. SQMI antibody may be useful in biological and clinical studies of the head and neck region.
Prostaglandin and hydroxyeicosatetraenoic acid synthesis by human mesenchymal tumors
Authors: Knazek Richard A. , Yee Carole L. , Costa Jose
Published: February 2007

The metabolism of arachidonic acid was investigated by radioimmunoassay and chromatographic techniques in 5 sarcomas and one embryonal carcinoma of human origin maintained as transplantable tumors in nude mice. The results obtained indicate that: (1) the absolute quantities of arachidonic acid metabolites produced by a given tumor varied between experiments but the overall distribution pattern of these products, in general, remained constant from passage to passage; (2) each tumor showed a different arachidonic acid metabolite profile in quality and quantity; (3) 2 sarcomas of the same histological type could be clearly distinguished by their arachidonic acid metabolites; (4) the predominant product in all tumors was 12‐HETE3 or 15‐HETE, whereas thromboxane A2 was synthesized in low quantities by all tumors; (5) PGF2α was synthesized at the highest rate by an alveolar rhabdomyosarcoma; (6) PGE2 synthesis was highest in a malignant fibrous histiocytoma; and (7) total prostaglandin synthesis was low in the chondrosarcoma and synovial‐cell sarcomas.

All results reported in this study are for the complete tumor which includes both neoplastic and stromal cells. The role that these products play in the biological behavior of mesenchymal tumor cells and normal tissues of the host remains to be determined.
Host cell range of adult t‐cell leukemia virus I. Viral infectivity and binding to various cells as detected by flow cytometry
Authors: Sinangil Faruk , Harada Shinji , Purtilo David T. , Volsky David J.
Published: February 2007

Adult T‐cell leukemia virus is the member of a human type‐C retrovirus family (HTLV) found to be associated with adult T‐cell leukemia (ATL) in Japan. In our study, HTLV was isolated from the MT‐2 cell line, purified on sucrose gradient and labelled with fluorescein‐isothiocyanate (FITC‐HTLV). The protein pattern of the virus was determined by SDS‐gel electrophoresis and assured by Western blotting using ATL patient serum. Fresh human lymphocytes, separated Band T cells, mouse and rabbit lymphocytes, mouse fibroblasts, and 13 different tumor cell lines were tested in parallel for binding of FITC‐HTLV and infectability by the virus. Virus binding to cell receptors was assayed by flow cytometry. Successful infection was monitored by following the expression of HTLV determined antigen (HTLA). Most of the cells bound FITC‐HTLV at levels ranging from 5% to 130% of the MT‐2 cell binding. Only fresh human T, mouse and rabbit lymphocytes were infectable by cell‐free virus preparations. The results demonstrate that HTLV receptors are present on different types of cells of both human and animal origin, and that infection by the virus is restricted to fewer host cells but not limited to a specific class of human lymphocytes.
Changes in plasma hormone profiles after tumor transplantation into syngeneic and allogeneic rats
Authors: Besedovsky Hugo O. , Rey Adriana Del , Schardt Martin , Sorkln Ernst , Normann Sigurd , Baumann Joyce , Glrard Jürg
Published: February 2007

Transplantation of 2 chemically (DMBA, MCA)‐induced tumors into syngeneic female or male DA strain rats elicited hormonal changes during tumor growth. Plasma levels of 7 different hormones were studied. Tumor cells in syngeneic recipients produced a biphasic decrease in insulin, an early increase in prolactin, and a late‐phase decrease in thyroxine. Corticosterone decreased in female tumor bearers but increased in males. This difference may reflect differences in the tumors transplanted. Male rats had a decrease in testosterone during the late phase of tumor growth, while females had a biphasic decrease in progesterone and a late‐phase increase in growth hormone. The tumors used were moderately immunogenic in syngeneic recipients. However, tumor transplantation to allogeneic recipients produced an early decrease in growth hormone and no change in insulin, corticosterone or thyroxine. Further, transplantation of normal liver cells to syngeneic or allogeneic recipients produced no hormonal abnormalities.

This study demonstrates that hormonal changes which are not observed with normal cells or allogeneic tumor transplantation can occur within 2 days of syngeneic tumor transplantation. Progressive tumor growth is characterized by a worsening endocrine imbalance which involves multiple hormone systems.
Systemic adoptive transfer of immunity and low‐dose irradiation eradicate metastases of 13762a rat mammary adenocarcinoma
Authors: Kreider John W. , Bartlett Gerald L. , Christensen Neil D. , Welsh Patricia
Published: February 2007

Rats cured of poorly immunogenic 13762A tumor by a combination of surgery and cyclophosphamide (CY) treatments produced peritoneal exudate cells (PEC) that prevented tumor growth when transferred to naive recipients, but they were ineffective against established tumor. A highly immunogenic 13762A clone (18A) induced PEC lymphocytes that completely reversed the growth of established primary tumor and of lymph‐node metastases. 18A‐immune PEC alone strongly inhibited tumors of 7 days' duration, but only moderately suppressed 14‐day tumors, and had no effect on 21‐day tumors. Irradiation (450 R) of rats prior to tumor transplantation improved the effectiveness of the PEC given at 7 days, but the benefit had gone by 14 days. Long‐term T‐cell depletion prior to tumor challenge allowed PEC inhibition of 7‐ and 14‐day tumors, but not 21‐day tumors. The most potent strategy was the administration of 450 R followed immediately by immune PEC. When rats with 21‐day tumors were so treated, the metastases grew temporarily to a maximum diameter of 2‐5 cm and then completely regressed. We concluded that a combination of immune T cells and 450 R can cure established, massive metastases, probably through a combination of an increase in the numbers of T‐cell effectors and elimination of suppressor cells.
Production of PDGF‐like growth factor by breast cancer cell lines
Authors: Rozengurt Enrique , Sinnett‐Smith James , Taylor‐Papadimitriou Joyce
Published: February 2007

The breast cancer cell line T47D produces factors which show mitogenic activity for 3T3 cells. Here we describe the partial purification of one of these factors and show that it has properties similar to plateletderived growth factor (PDGF). The T47D factor is a heat‐stable hydrophobic protein with a molecular weight of around 30,000, which inhibits the binding of 125I‐EGF in a temperature‐dependent manner. This 30 kd protein does not act synergistically with PDGF or fibroblast‐derived growth factor (FDGF; also PDGF‐like) in stimulating DNA synthesis; moreover, like these two factors, its mitogenic activity can be inhibited by an antiserum raised against human PDGF. A PDGF‐like growth factor was also found in the serum free medium of the breast cancer cell line MDA‐MB157. Since PDGF acts on mesenchymal cells, the production of PDGF like growth factors by breast cancer cells suggests a basis for the intense stromal reaction seen in human breast cancers.
Selection and characterization of monoclonal antibodies to the idiotype‐like structure of an interleukin‐2‐producing human leukemia t‐cell line
Authors: Moretta Alessandro , Pantaleo Giuseppe , Lopez‐Botet Miguel , Moretta Lorenzo
Published: February 2007

A variant of the Jurkat leukemia cell line termed JA3 (surface phenotype: T11 +, T3 +, T4‐, T8‐, T6‐, T1 +, 3A1 +, HLA‐DR‐, Tac‐, 4FZ+) has been used for mouse immunization and production of monoclonal antibodies (MAbs) to molecules carrying clonotypic determinants that are thought to serve as receptor for antigen on human T cells. JA3 had been selected because of its ability to release large amounts of IL‐2 following stimulation with phytohemagglutinin (PHA) or anti‐T3 antibody in the presence of phorbolmyristate acetate (PMA). This functional property has been exploited for screening of MAbs potentially directed to idiotype‐like structures of JA3 cells. Thus supernatants of hybridomas (obtained by fusing mouse splenocytes with P3‐UI myeloma cells) were analyzed for their ability to induce JA3 cells to release IL‐Z in the presence of PMA. Four stimulatory antibodies reacted with JA3 but not with polyclonal T‐cell populations, T‐cell clones, or T and B tumor cell lines as assessed by indirect immunofluorescence and fluorescence‐activated cell sorter (FACS) analysis. All 4 antibodies immunoprecipitated the same disulphide‐linked heterodimeric molecules having a molecular mass (M′) of approximately 85,000 under non‐reducing conditions that was resolved in Z major peptides of 40,000 and 45,000 under reducing conditions. These data indicate that these antibodies (termed anti‐JTi) were directed to the clonotypic‐restricted structures of the JA3 T‐cell ‐ receptor molecules. Unlike the anticlonotypic antibodies described so far, anti‐JTi MAbs were capable of triggering IL‐Z production even in unbound, soluble form, in the absence of adherent cells or PMA. Competitive inhibition experiments, in which 35S‐la‐belled anti‐JTi MAbs have been used, provided evidence that they may be directed against different epitopes on the same clonotypic structure.
The establishment and characterization of a new balb/c angiosarcoma tumor system
Authors: Zvibel Isabel , Raz Avraham
Published: February 2007

A BALB‐3T3/A31 untransformed cloned cell line and 3 selected variants derived from this parental cell line, expressing 3 increasingly malignant phenotypes, have been established and characterized in vivo and in culture. This new tumor series, identified as angiosarcoma, consists of an anchorage‐independent nontumorigenic cell clone and 2 sublines exhibiting tumorigenic and metastatic properties. Morphological examination revealed that the 3 transformed cell variants differed from the normal parental cells and were not contact‐inhibited. Karyotype and rate of cell proliferation in culture were similar for all the cell variants. Cytoskeletal visualization by immunofluorescence staining revealed that the tumorigenic and metastatic cell lines expressed an altered organization of actin cables and a smaller number of vinculin‐containing focal contacts. Lactoperoxidase iodination of cell surface proteins showed the appearance of an Mγ 86,000 protein in the tumorigenic and metastatic cell variants. Analysis of cell‐surface glycoproteins demonstrated an increased sialylation of Mγ 66,000 and Mγ 62,000 glycoproteins in the transformed, tumorigenic and metastatic cell lines. This angiosarcoma tumor model system allows investigation of cellular characteristics which might be relevant to specific stages in tumor progression.
Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host
Authors: Caignard A. , Martin M. S. , Michel M. F. , Martin F.
Published: February 2007

From a single, chemically‐induced rat colonic carcinoma, two subpopulations of tumor cells have been isolated. When injected into syngeneic rats, TR cells give rise to progressive tumors in most of the animals, whereas TS cells give rise to no tumors or to tumors which regress in less than 30 days. TS cells inhibit the growth of TR tumors, whether they are injected before TR cells or simultaneously, at a different site or mixed with the TR cells. Lymph nodes and spleen lymphocytes from animals having rejected TS tumors also inhibit TR‐cell growth. On the other hand, TS cells are able to give rise to progressive tumors when they are injected into rats bearing established TR tumors. Lymph nodes and spleen cells of TR tumorbearing rats are able to enhance TS cell growth. These results suggest that subpopulations of cancer cells contained in the same tumor interact with each other through their effect on the host immune system. The growth of a whole tumor probably depends not only on the growth potential of each constituent subpopulation, but also on the interaction between the subpopulations themselves.
Influence of reproductne history on age at diagnosis of breast cancer and prognosis
Authors: Wang D. Y. , Allen D. S. , Bulbrook R. D. , Rubens R. D. , Millis R. R. , Chaudary M. A. , Hayward J. L.
Published: February 2007

The effect on age at breast cancer diagnosis of age at menarche, age at first baby, parity and age at menopause has been determined for 739 unselected patients diagnosed between 1975 and 1980 as having operable breast cancer. Age at diagnosis was significantly and positively associated with ages at menarche, first baby and menopause. The average number of children significantly declined with increasing age at diagnosis. This was largely due to a change in the proportion of patients who were nulliparous (15% in women aged 41‐50 years compared to about 30% in those over 60 years). A group of 1,989 normal women whose reproductive history was also collected between 1975 and 1980 showed similar trends between age and age at menarche, age at first baby and parity as the patients. Thus it appears that these reproductive parameters do not alter the time of onset of breast cancer but could be explained by temporal changes in reproductive patterns. There was no significant correlation between age at menopause and age at diagnosis for patients whose age at menopause was no more than 54 years and age at diagnosis no less than 55 years, respectively. It is therefore unlikely that age at menopause affects age at diagnosis. Postmenopausal patients with 3 or more children had a significantly shorter disease free interval and lower survival rate than those with less children. None of the other parameters was associated with prognosis.
Partial purification and characterization of a vascular permeability factor secreted by a human colon adenocarcinoma cell line
Authors: Lobb Roy R. , Key Marc E. , Alderman Edward M. , Fett James W.
Published: February 2007

The established human colon adenocarcinoma cell line, HT‐29, secretes a vascular permeability factor (VPF) in vitro. The factor has been purified from serum‐free conditioned medium by acidification, cation‐exchange, and reverse‐phase and anion‐exchange high‐performance liquid chromatography. The VPF is a non‐glycosylated acidic protein of apparent molecular weight 45,000, and is at least 4 orders of magnitude more potent than histamine as an inducer of vascular permeability. Its biological activity is unaffected by soybean trypsin inhibitor or by inhibitors of histamine, kinins, prostaglandins, or acid proteases. The VPF induces vascular permeability within minutes, which suggests a direct effect on the endothelial cell.
Structure‐activity relationship in the induction of Epstein‐Barr virus by teleocidin derivatives
Authors: Koshimizu Koichi , Hagiwara Nobuyuki , Irie Kazuhiro , Ito Yohei , Tokuda Harukuni , Murao Sawao , Hayashi Hideo
Published: February 2007

New derivatives of (‐)‐indolactam V (Fig. I), which have the basic ring‐structure of teleocidins without the monoterpenoid moiety, were prepared and their Epstein‐Barr virus early antigen (EBV‐EA)‐inducing activity was tested. (‐)‐14‐O‐Alkyl indolactam Vs (2 and 3) showed little induction of EBV‐EA, while (‐)‐14‐dehydroxyindolactam V (4) and (‐)‐14‐chloroindolactam V (5) proved to be potent EBV‐EA inducers, though their activities (EC50) were about 10 times weaker than that of (‐)‐indolactam V (1). These results indicate that the hydroxyl group at C‐14 is not indispensable for EBV‐EA induction and can be replaced. The activities (EC50) of (‐)‐I‐N‐methyl, (‐)‐I‐N‐ethyl, and (‐)‐I‐N‐butyl indolactam V (10, 11, and 12) were about 5 times weaker than that of (‐)‐indolactam V (1), while (‐)‐I‐N‐hexyl and (‐)‐I‐N‐octyl indolactam V (13 and 14) were even less active, suggesting that the free imino group of the indole ring in (‐)‐indolactam V (1) plays an important role in the activity, and that the activity cannot be enhanced by alkylation at the N‐I position of (‐)‐indolactam V (1).
Tiadenol‐mediated induction of peroxisomal enzymes in cultured C3H/10T1/2CL8 cells and in chemically transformed C3H/10T1/2 MCA16 cells
Authors: Berge Rolf K. , Lillehaug Johan R.
Published: February 2007

The levels of peroxisomal enzyme activities in cultured C3H/10T1/2 CL8 cells and in chemically transformed C3H/10T1/2 MCA16 cells were studied after treatment with tiadenol and niadenate, two hypolipidemic drugs which are both carcinogenic and cause peroxisome proliferation in vivo. Administration of these peroxisome proliferators to the cells resulted in large increases in specific palmitoyl‐CoA hydrolase, carnitine acetyl‐transferase, and catalase activities. A reproducible induction of cyanide‐insensitive palmitoyl‐CoA oxidative activity was observed 5 and 9 days after initiation of tiadenol treatment. Basal activity was 0.16 nmole/min/mg protein compared to 0.95 nmole/min/mg protein in cells treated with 18 μM tiadenol (cytotoxicity of about 25%) for 9 days. The enzyme activities were more increased in the transformed MCA 16 cells than in the non‐transformed cells and the order of increase in enzyme activities was: niadenate > tiadenol. In non‐transformed cells, the specific activity of palmitoyl‐CoA hydrolase was enhanced approximately 2.1‐fold within 4 days after tiadenol treatment. During this time period the enzyme activity was constant in untreated cells, but decreased during longer incubation periods. The enhancement of palmitoyl‐CoA hydrolase, carnitine acetyl‐transferase and catalase activities was dose‐related over a concentration range of 2 to 20 μM tiadenol, depending on the enzyme assayed. Tiadenol concentrations above 10 μM were increasingly cytotoxic, while 18 μM niadenate had no toxic effect on the C3H/10T1/2 C18 cells. Moreover, the stimulation of the 3 enzyme activities by the peroxisome proliferators were inhibited by cycloheximide. Neither of the two cell lines contained any appreciable urate oxidase activity. The responses of these cells to hypolipidemic drugs show that they constitute a useful system for studies on the role of peroxisomes in lipid metabolism and the relationship between hypolipidemic activity and carcinogenic potential of these drugs.
Lung colonization and metastasis by disseminated b16 melanoma cells: H‐2 associated control at the level of the host and the tumor cell
Authors: Taniguchi Kazuto , Käarre Klas , Klein George
Published: February 2007

We have studied the experimental metastasis of H‐2+ and H‐2− melanoma sublines in H‐2b/b and H‐2a/b hosts by enumerating pulmonary colonies 20–50 days after i.v. inoculation of tumor cells. In H‐2b/b hosts, the H‐2+ „B 16‐S”︁ cells gave rise to a moderate number of metastatic colonies (mean: 6.3 ± 6). The „BL 16‐L”︁ sublines that had lost the expression of MHC class I antigens, according to FACS‐analysis and quantitative absorption tests, gave no metastases under the same conditions. Pretreatment of the H‐2+ met+ B 16‐S with interferons (beta or alpha + beta) increased their H‐2 antigen expression and the number of metastatic colonies (mean: 25 ± 16). Interferon pretreatment of B16‐L cells partially restored their H‐2b expression and induced them to form a small number of metastatic colonies. The reduction in pulmonary colonization by the H‐2 negative B16‐L cells could be attributed to their rapid elimination by natural killer cells, already observed within 24 hr of inoculation of radiolabelled cells. H‐2− B16‐L cells were more susceptible than H‐2+ B16‐S cells to in vitro lysis by poly I:C‐treated splenocytes, and they acquired full metastatic abilities if the hosts were treated with anti‐asialo GM‐I serum. In H‐2a/b heterozygous hosts, the H‐2+ B16‐S cells also failed to metastasize. Reduced pulmonary colonization was evident by 24 hr after injection in comparison with H‐2b/b hosts, and could be reversed by anti‐asialo GM‐I treatment of the hosts. In vitro, H‐2a/b splenocytes were more cytotoxic to the B16 cells than syngeneic effectors. The results are discussed in relation to a recent hypothesis on a surveillance mechanism for elimination of cells on the basis of their lack (or insufficient expression) of host MHC genes.
A potential role for the extracellular matrix glycoprotein laminin in macrophage‐tumor‐cell interactions
Authors: Huard Thomas K. , Baney Jill L. , Wood James F. B. , Wicha Max S.
Published: February 2007

Although cell surface molecules are thought to be involved in macrophage (MO)‐tumor‐cell recognition, the nature of these molecules remains unknown. In this study we have shown that the glycoprotein laminin may facilitate macrophage‐tumor‐cell binding. Macrophage binding to tumor cells was assessed by measuring the adherence of radiolabelled 3‐MCA2 induced malignant fibrosarcoma cells to syngeneic peritoneal MOs. Addition of exogenous laminin promoted the binding of a weakly metastatic subline of these tumor cells by 31‐68%. These weakly metastatic tumor cells express negligible endogenous cell‐surface laminin but display specific cell‐surface receptors for binding soluble laminin. Exogenous laminin promoted MO binding of these tumor cells whether it was present during the assay or whether the tumor cells were pretreated with the laminin. This increase in binding was blocked by anti‐laminin antibody. In contrast, MO binding of a strongly metastatic variant of the same tumor was not enhanced by the addition of exogenous laminin. This highly malignant fibrosarcoma line already expressed endogenous cell‐surface laminin. Since the MOs were found to specifically bind <125>I‐laminin, the interaction between laminin‐bearing tumor cells and MOs may be mediated via a specific MO plasma membrane receptor. Thus, the expression of cell surface laminin and its receptors on both tumor cells and MOs may provide a mechanism for promoting MO‐tumor‐cell binding.
Detection of a retrovirus‐related glycoprotein in immune complexes from patients with hematopoietic disorders
Authors: Jacquemin P. C. , Striuckmans P.
Published: February 2007

Human sera from normal and leukemic individuals were found to contain various amounts of an antigen with determinants related to pI5E and reverse transcriptase of retroviruses. Using a specific monoclonal antibody and the immuno‐affinity purified antigen, we surveyed a series of sera and plasmas from normal individuals and hematological patients by competition radioimmunoassays and binding assays directed against this specific protein. It was detected in all the samples at various levels. The level of this 74‐kd glycoprotein appeared to be related to a stimulation of the hematopoietic system. No free antibodies were found that could recognize the labelled purified antigen. Only immune complexes prepared from the blood of some hematological patients contained the specific antigen, but complexes prepared from the blood of normal individuals did not.
Prospective studies on nasopharyngeal carcinoma in epstein‐barr virus IgA/VCA antibody‐positne persons in Wuzhou city, china
Authors: Zeng Y. , Zhang L. G. , Wu Y. C. , Huang Y. S. , Huang N. Q. , Li J. Y. , Wang Y. B. , Jiang M. K. , Fang Z. , Meng N. N.
Published: February 2007

A serological mass survey was carried out in Wuzhou City in 1980, 1,136 IgA/VCA‐positive persons being followed up for 4 years. Altogether 35 NPC cases were detected, of which 15 (43%) were in stage I and 17 (48.5%) in stage II, early cases (I + II) thus amounting to 91.5%. The detection rate of early cases was 2.9 times higher than in our outpatient clinic. IgA/VCA antibody could be detected 16–41 months prior to clinical diagnosis of NPC. We conclude that, if IgA/VCA‐positive individuals are examined routinely once a year, NPC can be detected in the early stages of evolution. The annual detection rate of NPC in IgA/VCA antibody‐positive individuals was 31.7 times higher than that of the annual incidence of NPC in the general population in the same age group, while during the 4‐year follow‐up period the incidence was 7.5 times higher than in the general population for the same age group. These results further indicate that EB virus plays an important role in the development of NPC, and that serological screening and follow‐up studies are valuable for the early detection of NPC.
HTLV‐I is endemic in Southern Italy: Detection of the first infectious cluster in a white population
Authors: Manzari Vittorio , Gradilone Angela , Barillari Giovanni , Zani Massimo , Collalti Enrico , Frati Luigi , Pandolfi Franco , De Rossi Giulio , Liso Vincenzo , Babbo Pasquale , Guroff Marjorie Robert
Published: February 2007

Human T‐cell leukemia virus (HTLV‐I) infection is observed among black and Japanese populations in well‐delimited endemic spots in association with a high incidence of adult T‐cell leukemia (ATL).

We present evidence of HTLV‐I infection in two ATL patients from southeastern Italy who have not travelled and who have no known relations abroad, and in 8% of non‐leukemic controls from the same area. Thus, populations exhibiting HTLV‐I infection appear more widespread than supposed up to now.
Expression of burkitt lymphoma‐associated antigen (defined by the monoclonal antibody 38.13) on both normal and malignant germinal‐centre B cells
Authors: Murray L. J. , Habeshaw J. A. , Wiels J. , Greaves M. F.
Published: February 2007

Monoclonal antibody 38.13 was raised against the Burkitt lymphoma cell line Daudi and has been previously shown to recognize a globotriaosylceramide (pk) determinant expressed selectively on Burkitt and a few other B‐cell lymphomas. We report here that 38.13 binds to a subset of normal B lymphocytes in germinal centres of secondary lymphoid follicles as well as to blood vessels. In malignant populations equivalent to various developmental compartments of the B‐cell lineage, only those with a follicular phenotype express the pk determinant at detectable levels. The expression of this tumour‐associated antigen, in common with many others, is therefore regulated in concert with cell lineage and maturation status.
Multiple epitopes on a human breast‐carcinoma‐associated antigen
Authors: Price M. R. , Edwards S. , Owainati A. , Bullock J. E. , Ferry B. , Robins R. A. , Baldwin R. W.
Published: February 2007

The monoclonal antibody (MAb) NCRC‐11 identifies an epitope expressed variably in human breast cancer. The degree of expression of this epitope in primary operable tumours is closely related to the subsequent clinical course of the disease (Ellis et al., 1985). The target antigen for NeRC‐11 was isolated from subcellular membranes of breast carcinomas and purified by immunoadsorbent chromatography. NCRC‐11 epitopes were expressed upon a large glycoprotein of more than 400 kd. This material was susceptible to degradation by pronase and papain and contained Nacetylglucosamine, as indicated by its binding to wheat‐germ agglutinin. The NCRC‐11‐defined antigen expressed epitopes for the anti‐human milk‐fat globule membrane antibodies HMFG‐1 and HMFG‐2, and other antibodies against epithelial membrane antigens (EMA, LICR‐LON‐M8). The reactivity of these antibodies with tumour membranes was also similar, but not identical, to that of the NCRC‐11 antibody. In competitive binding‐inhibition assays these antibodies partially inhibited the binding of 125I‐NCRC‐II antibody to antigen, suggesting that the epitopes involved are topographically closely associated. Sandwich immunoassays demonstrated that NCRC‐11 epitopes are likely to represent repeated structures of the NCRC‐11 antigen. The findings presented are interpreted as indicating that the NCRC‐11 antigen expresses a variety of epitopes which are associated with normal differentiation and malignant change.
Papillomavirus DNA in human tongue carcinomas
Authors: De Villiers E.‐M. , Weidauer H. , Otto H. , Zur Hausen H.
Published: February 2007

Seven biopsies from different carcinomas of the tongue were analyzed for human papilloma virus (HPV) sequences by Southern blot analysis. After hybridization with various types of human papilloma viruses, 1 tumors were found to be positive. Whereas DNA from one tumor hybridized with HPY 2 DNA under conditions of high stringency, the 2 other positive biopsies contained HPV 16 DNA. All positive tumors revealed high copy numbers of the respective DNA. The cleavage pattern of the HPV‐2‐positive tumor differed from the established HPV 2 prototypes. Minor differences from the HPV 16 prototype were also noted in one of the HPV‐16‐positive tongue carcinomas.