bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor‐cell lysis by in‐situ‐activated human peripheral‐blood mononuclear cells
Authors: Smans Karine A. , Hoylaerts Marc F. , Hendrickx Herman F. , Goergen Martine J. , De Broe Marc E. 
Published: February 2007

AbstractA heteroconjugate (HC) was synthesized between OKT3 and monoclonal antibody (MAb) 7E8, which specifically reacts with the tumor marker placental alkaline phosphatase (PLAP). Similarly to OKT3, in vitro, the HC induced a dose‐dependent proliferation response of human peripheral‐blood mononuclear cells (PBMCs) and, in concert with rlL‐2, it progressively activated T cells over a 4‐day period. In co‐cultures of continuously activated PBMCs and M04 tumor cells (non‐MHC‐restricted mouse fibroblasts transfected with the cDNA for PLAP), the HC (25 ng/ml), again acting in concert with rlL‐2, induced specific lysis of the MO4 cells. This process occurred progressively over 2 to 3 days and was monitored from the release in the supernatant fluid of cellular 3H‐L‐leucine, but also from analyses involving the remaining non‐lysed cancer cells, i.e., by estimates of their protein content, by measurements of their viability, and most accurately by determinations of their PLAP content. Antibody 7E8 by itself induced a weak tumor‐cell lysis (ADCC), potentiated by the addition of rlL‐2. However, after 7 days of PBMC‐preactivation with the HC and rlL‐2, antibody 7E8 no longer mediated any ADCC, whereas the HC‐dependent lysis was further potentiated. The observed proliferation of T cells and development of cytotoxicity at low concentrations of HC and rlL‐2 support the idea that a moderate but continuous T‐cell activation combined with T‐cell targeting is sufficient for the induction of progressive and efficient tumor‐cell lysis.
Binding of epidermal growth factor‐dextran conjugates to cultured glioma cells
Authors: Andersson Annelie , Holmberg Anders , Carlsson Jörgen , Carlsson Jan , Pontén Jan , Westermark Bengt 
Published: February 2007

AbstractSome gliomas, melanomas and squamous carcinomas have large numbers of EGF receptors which could, in these cases, be used for targeting with toxic agents. We investigated whether EGF could be conjugated to dextran, which is a suitable carrier for toxic agents, without losing its ability to bind to the receptor. Dextran of 20 kDa molecular weight was activated with l‐cyano‐4‐dimethylamino pyridinium tetrafluoroborate (CDAP) yielding highly active pyridinium‐isourea derivatives. EGF was coupled to the activated dextran through the amino terminus and glycine was added to block residual activity. The EGF‐dextran conjugate was, after purification on Sephadex G25 and Sephacryl 200 columns, tested for its receptor binding properties on human malignant glioma, U343MgaC12:6, cells. The conjugate inhibited binding of l25I‐EGF in a competitive assay, showing that the binding was receptor‐specific. Dextran conjugated with glycine, without EGF, had no inhibitory effect. The conjugate was radio‐labelled either on the EGF part with 125I or on the dextran part with 3H‐glycine, and the internalization patterns were compared to the internalization of 125I‐EGF. The radioactivity of the conjugates remained cell‐associated for more than 20 hr, regardless of whether the radioactivity was on the EGF or on the dextran part, while the radioactivity of unconjugated EGF rapidly disappeared from the cells. Most of the cell‐associated radioactivity was, at all analysed time intervals, located intracellularly. Thus, it seems promising to use dextran, conjugated with EGF, as a carrier of, for example, toxic radioactive nuclides.
Enhancement of natural‐killer‐cell susceptibility of human breast‐cancer cells by estradiol and v‐Ha‐ras Oncogene
Authors: Screpanti I. , Felli M. P. , Toniato E. , Meco D. , Martinotti S. , Frati L. , Santoni A. , Gulino A. 
Published: February 2007

AbstractNatural killer (NK) cells are putative components of the cellular immune response to transformed cells. Since both estradiol treatment and ras‐oncogene overexpression enhance tumorigenicity of hormone‐dependent breast‐cancer cells, we studied the effects of estrogen and of the activated v‐Ha‐ras oncogene on NK susceptibility of MCF‐7 human breast‐cancer cells. MCF‐7 cells were sensitive to cytolysis mediated by resting and IL2‐activated peripheral‐blood nonadherent lymphocytes. Lysis appeared to be mediated by NK cells, since it was abrogated by treatment of effector cells with α‐CD16 monoclonal antibody (MAb) plus complement (c'). Estradiol treatment of MCF‐7 cells was able to significantly increase their sensitivity to the lysis by IL2‐activated and unactivated peripheral‐blood lymphocytes, as early as 24 hr throughout 10 days of hormone treatment. Hormone‐insensitive, estrogen‐receptor‐negative breast‐cancer cells (BT20) did not change their NK susceptibility after estradiol treatment. Increased NK susceptibility was also observed in v‐Ha‐ras‐transfected and oncogene product overexpressing MCF‐7 cells (MCF‐7‐ras) with respect to cells transfected with the selectable gene marker gpt alone (MCF‐7‐gpt). Overexpression of v‐Ha‐ras appeared to be able to bypass the need for estrogen to increase NK susceptibility, since estradiol‐treated MCF‐7‐ras cells were not lysed more than untreated MCF‐7‐ras cells. The enhancement of NK susceptibility observed after both estradiol treatment and v‐Ha‐ras overexpression suggests that the hormone‐mediated and the ras‐oncogene‐mediated signalling systems share events involved in the control of tumor‐cell/host‐effector‐cell interactions.
Growth regulation of the AML‐193 leukemic cell line: Evidence for autocrine production of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and inhibition of GM‐CSF‐dependent cell proliferation by interleukin‐1 (IL‐1) and tumor necrosis factor (tnfα)
Authors: Kindler Vincent , Shields John , Ayer Dominique , Mazzei Gonzalo J. 
Published: February 2007

AbstractThe human leukemic cell line AML‐193 was tested for its proliferative response to endogenously produced autocrine factors and to a variety of cytokines and colony‐stimulating factors. Cells grown in the absence of GM‐CSF incorporated tritiated thymidine, and this was partially reversed by adding neutralizing anti‐GM‐CSF antibodies to the culture medium, suggesting that it was due, at least in part, to autocrine GM‐CSF production. This was confirmed by immunopurification of a GM‐CSF‐like activity from cell supernatant of AML‐193 cells grown in serum free medium in the absence of exogenous GM‐CSF. When AML‐193 cells were cultured with GM‐CSF in combination with other cytokines, lnterleukin‐1 α and β (IL‐I α and β), lnterleukin‐3 (IL‐3), lnterleukin‐6 (IL‐6), granulocyte colony‐stimulating factor (G‐CSF) and tumor necrosis factor a (TNFα), none of them affected the concentration of GM‐CSF required to induce 50% of maximum proliferation (D50). However, the maximum proliferation induced by GM‐CSF alone was drastically decreased by IL‐I α, IL β and TNFα. Inhibition caused by exposure of the AML‐193 to IL‐I for up to 24 hr was reversible, ruling out a direct cytotoxic effect.
Ornithine decarboxylase activity and polyamine content in adenocarcinomas of human stomach and large intestine
Authors: Berdinskikh N. K. , Ignatenko N. A. , Zaletok S. P. , Ganina K. P. , Chorniy V. A. 
Published: February 2007

AbstractOrnithine decarboxylase (ODC) activity and differential polyamine composition have been studied in macroscopically normal mucosa, adjacent mucosa, and neoplastic tissue of 95 patients with adenocarcinomas of stomach and large intestine. In tumors, we found increased ODC activity and polyamine content as compared with surrounding mucosa. ODC activity in macroscopically normal tissue of patients with tumors of stomach and large intestine increased as the disease progressed. An inverse relationship was observed between ODC activity in adenocarcinomas and differentiation.
The decline in the incidence of stomach cancer in sweden 1960‐1984: A birth cohort phenomenon
Authors: Hansson Lars‐Erik , Bergström Reinhold , Sparjén PÄR , Adami Hans‐Olov 
Published: February 2007

AbstractTrends in the incidence of stomach cancer among 52,604 patients notified to the National Swedish Cancer Registry in 1960 through 1984 were analysed. Age‐standardized incidence rates declined throughout the period, from 47.1 to 24.6 per 105 in males and from 23.8 to 12.7 per 105 in females. Among males the decline in incidence was more pronounced in younger age strata, 35‐54 years, while in females it reached a maximum at ages 70‐74 years. In a multivariate analysis the age‐cohort model adequately represented the data and there was no reason to separate the effects of the full age‐period‐cohort model. Compared with the cohort born in 1876‐1884, the relative risk of developing stomach cancer was 0.46 (95% Cl:0.44‐0.48) in males and 0.39 (95% Cl:0.37‐0.42) in females born in 1906‐1914. This supports the view that the declining incidence is due to a change in the exposure of the population to aetiological factors of stomach cancer and not to refinement of the diagnosis and classification of abdominal tumours. The results also imply that exposure to aetiological factors early in life together with a long induction period is of importance in the development of stomach cancer.
Risk factors for penile cancer: Results from a case‐control study in china
Authors: Brinton Louise A. , Jun‐Yao Li , Shou‐De Rong , Huang Suzanne , Sheng Xiao Bin , Bai‐Gao Shi , Zhe‐Jun Zhu , Schiffman Mark H. , Dawsey Sanford 
Published: February 2007

AbstractAn epidemiologic study of penile cancer involving 141 cases and 150 community controls was undertaken in a high‐risk area in China. Personal interviews, as well as physical examinations among the prospectively ascertained subjects, enabled evaluation of a variety of potential risk factors. Strongly related to risk were conditions restricting the motility of the foreskin, including phimosis or paraphimosis, particularly when so severe that circumcision was used for treatment. Poor hygiene practices also appeared to increase risk, particularly as evidenced by detection of smegma on physical examination, although it was difficult to decipher whether this association was etiologic or merely a consequence of disease. A sexual relationship outside of marriage was associated with a RR of 1.7, and appeared to be a more important discriminator than number of lifetime sexual partners. Risk was increased among subjects reporting previous genital conditions, particularly sexually transmitted diseases, and physical examinations revealed the appearance of genital warts among 13 cases vs. I control. Interviews with wives of study subjects failed to provide evidence of a “female factor” in the etiology of penile cancer. This study supports the need for further evaluation of the role of hygiene and sexually transmitted agents in the etiology of penile cancer.
Scid mouse model of epstein‐barr virus‐induced lymphomagenesis of immunodeficient humans
Authors: Purtilo David T. , Falk Kerstin , Pirruccello Samuel J. , Nakamine Hirokazu , Kleveland Kimberly , Davis Jack R. , Okano Motohiko , Taguchi Yuichi , Sanger Warren G. , Beisel Kirk W. 
Published: February 2007

AbstractImmunodeficient humans are at very high risk of developing Epstein‐Barr virus (EBV)‐induced lymphomagenesis. Severe combined immunodeficient mice (SCID) have been shown to develop lymphoproliferative disease (LPD) following transfer of peripheral blood leukocytes (PBL) with latent EBV. To study mechanisms of lymphomagenesis, we compared results of engraftment of PBL from normal donors and immunodeficient donors with X‐linked lymphoproliferative disease (XLP). Graft‐versus‐host disease (GVHD) developed in 6 of 10 SCID mice 4 to 8 weeks following transfer of PBL from normal donors. In contrast, none of 9 mice engrafted with PBL from XLP patients with T‐cell defects showed GVHD. LPD developed in mice regardless of the immune competence of the donors. The expression of EBV‐encoded proteins, results of immunophenotyping, and karyotyping of the LPD lesions revealed lethal oligoclonal LPD owing to transfer of latent EBV in B cells in mice engrafted with PBL from seropositive donors. Polyclonal LPD developed in mice engrafted with PBL from seronegative patients which were infected with B95‐8 virus 6 weeks after transfer of the cells. This model is useful for investigating mechanisms of EBV‐induced LPD in immunodeficient patients.
Isolation and characterization of a serologically defined tumour membrane antigen from a chemically‐induced rat sarcoma, HSN
Authors: Léger Olivier , Dunn Pamela L. , Coles B. , Dean C. J. 
Published: February 2007

AbstractPolypeptides containing the tumour antigenic determinant present on the external domain of a membrane antigen of the 3‐4 benzpyrene‐induced rat fibrosarcoma HSN have been isolated and purified. Following cleavage from intact cells with trypsin, the peptides were purified by immunoaffinity chromatography and SDS‐PAGE. Three polypeptides of molecular weight 120, 45 and 42 kDa were obtained that bound the specific rat monoclonal antibody (MAb) 11/160 in Western blots. Chemical analyses of the 45‐kDa fragment yielded the following sequence:

All 14 of the syngeneic MAbs prepared from rats bearing the HSN tumour competed with each other to bind to the specific antigen. Western blots of the purified tryptic fragments probed with 125I‐Ab, revealed that, while some of the MAbs (11/160, ALN/12/17 and ALN/9/94) recognized a sequential determinant, others (ALN/11/53, ALN/16/53, and AL/3/12) bound to a conformational epitope. It is concluded that the Ab, bind to distinct but overlapping epitopes.
Recombinant interferon alpha and gamma modulate the invasive potential of human melanoma in vitro
Authors: Hujanen E. S. , Turpeenniemi‐Hujanen T. 
Published: February 2007

AbstractWe have studied the effects of interferons (IFNs) on the attachment, collagenase IV activity, chemotactic migration and in vitro invasion of human melanoma (A2058) cells treated for various time periods with human recombinant interferon alpha (hrIFN‐α) or gamma (hrIFN‐γ). The cells treated with hrIFN alpha for a short time period attached more readily to purified basement membrane components, type IV collagen and laminin, than control cells. The stimulating effect of hrIFN gamma on the attachment was seen, however, when the cells were treated for a longer period of time (3 days) with this drug. The short‐term treatment with hrIFN alpha also enhanced the in vitro invasion of cells through a reconstituted basement membrane compared to findings with untreated control cells. Pre‐treatment of 3 days or more was, however, needed for hrIFN gamma to promote the invasion of A2058 cells. Both IFNs increased the secretion of basement membrane (type IV) collagen degrading metal‐loproteinase (collagenase IV) activity from human melanoma cells. Further, chemotaxis, i.e., directed migration of A2058 cells to laminin, was enhanced by both IFNs. In contrast, the attachment, collagenase IV activity, chemotaxis, and in vitro invasion were markedly inhibited when the cells were treated for an extended time period (7 days) with the IFNs. Interferons also inhibited cell proliferation after 4 days of exposure. These results suggest that time of treatment with interferons modulates the invasive capacity of human melanoma cells in vitro, causing initially a transient enhancement of invasion followed by an inhibition of invasive propensity after extended exposure to these drugs, and that different biochemical steps required for successful invasion are regulated in parallel by interferons alpha and gamma.
Tumor regression and induction of anti‐tumor immunity by local chemotherapy of guinea‐pigs bearing a line‐10 hepatocarcinoma
Authors: Claessen Anke M. E. , Valster Henriëtte , Bril Herman , Steerenberg Peter A. , Tan Ben T. G. , Scheper Rik J. 
Published: February 2007

AbstractLocal administration of a low dosage of the active cyclophosphamide derivative 4‐hydroperoxy‐cyclophosphamide (4‐HPCY) at the site of antigenic stimulation strongly enhances T‐cell‐mediated immune responses in both mice and guinea‐pigs. Such immunopotentiation is related to functional elimination of suppressor cells from the draining lymph nodes. In the present study we examined the potential immunotherapeutic effects of local cytostatic drug administration in strain‐2 guinea‐pigs bearing a line‐10 hepatocarcinoma. This tumor, when injected intradermally (106 cells) metastasizes within 7 days into the draining lymph node and untreated animals die within 60‐80 days from metastatic growth. In sensitization experiments, using irradiated line‐10 tumor cells, potentiation of delayed‐type hypersensitivity reactivity was observed with local administration of low dosages of 4‐HPCY. Intralesional treatment with increasing dosages of 4‐HPCY, when started 7 days after tumor‐cell inoculation and continued for 3 weeks, resulted in a dose‐dependent regression of the primary tumor. Cure rates of up to 75% were achieved. All cured animals showed strong delayed‐type hypersensitivity reactivity towards line‐10 cells and were resistant to a rechallenge with 106 line‐10 tumor cells. When treatment was started at a very late stage of the disease (day 14) only a small number of animals were cured. However, when local chemotherapy was preceded by one (non‐curative) systemic dose of cyclophosphamide, a 57% cure rate was obtained. Again, all cured animals showed strong delayed‐type hypersensitivity reactivity and protective immunity to line‐10 tumor cells. Tumor immunity was transferable to naive recipients with immune spleen cells and was T‐cell‐dependent. Other cytostatic drugs, selected for local immunopotentiating capacity, notably etoposide (VP16) and cis‐platinum (cis‐Pt) were similarly effective in the local chemotherapy protocol.
Combination of dietary factors in relation to breast‐cancer occurrence
Authors: Van T Veer Pieter , Van Leer Edith M. , Rietdijk Annelies , Kok Frans J. , Schouten Evert G. , Hermus Rudolph J. J. , Sturmans Ferd 
Published: February 2007

AbstractCombinations of dietary factors were studied in relation to breast‐cancer occurrence among 133 breast cancer cases and 289 population controls in The Netherlands. Dietary factors were classified according to their possible mechanism of action, i.e., relating either to the intestinal microflora (total fat, fiber, fermented milk products) or to the anti‐oxidant hypothesis (beta‐carotene, selenium and polyunsaturated fatty acids). From 6 interactions evaluated, the combination of high fiber intake and high intake of fermented milk products was the only one suggesting synergistic protection (age‐and‐fat‐adjusted OR for interaction = 0.48, 95% confidence interval (Cl) = 0.21 − 1.13). In order to estimate the extent to which the above dietary factors together might be related to breast cancer, subjects with a supposedly favorable dietary pattern (low fat intake, high fiber intake, high intake of fermented milk products; high intake of beta‐carotene and selenium, low intake of polyunsaturated fatty acids) were compared with subjects with an unfavorable dietary pattern. This resulted in an age‐adjusted odds ratio of 0.40 (95% Cl = 0.14–1.15), which was largely attributable to the combination of low intake of fat and high intake of fermented milk products and fiber (age‐adjusted OR = 0.33, 95% Cl = 0.15 − 0.73). The other factors did not appreciably affect the odds ratio. These analyses show in a quantitative way that a dietary pattern which combines low intake of fat and high intake of fiber and fermented milk products might provide substantial protection against breast cancer.
Oligoclonal T lymphocytes infiltrating human lung cancer tissues
Authors: Yoshino Ichiro , Yano Tokujiro , Yoshikai Yasunobu , Murata Mitsuhiro , Sugimachi Keizo , Kimura Genki , Nomoto Kikuo 
Published: February 2007

AbstractTo clarify the nature of tumor‐infiltrating lymphocytes (TILs), we investigated the possible clonality of the T cells in TILs freshly isolated from human primary lung cancer tissues by assessing the rearrangement pattern of the T‐cell receptor (TCR) gene P locus using Southern blotting. First, in phenotypic analysis, TILs represented different populations among corresponding peripheral blood lymphocytes (PBLs) with an increased proportion of CD20+ (B) cells as well as a decreased proportion of CD 16+ (natural killer) cells, and a variable CD4/ CD8 ratio. Considering the central role of T cells in immune responses, we analyzed TCR β gene rearrangement patterns in TILs and corresponding PBLs from 12 patients. In 10 of the 12 cases, TILs showed one or more TCR gene rearrangement bands with a predominance of the C.β2 gene, in which 2 types of common rearranged band were observed among the cases with different clinical profiles in terms of histological types and disease stage, with bands at about 9.5 kb in 7 and at 11.5 kb in 8 patients. On the other hand, predominant rearranged bands were hardly detected in corresponding PBLs except in 2 cases. From these results, we conclude that TILs in lung cancer tissues frequently contain oligoclonal T‐cell populations, which were probably sensitized by relatively common antigens at the tumor sites.
A phase‐i study of repeated therapy with radiolabelled antibody to carcinoembryonic antigen using intermittent or continuous administration of cyclosporin a to suppress the immune response
Authors: Ledermann J. A. , Begent R. H. J. , Massof C. , Kelly A. M. B. , Adam T. , Bagshawe K. D. 
Published: February 2007

AbstractThe anti‐mouse antibody response was examined in patients receiving repeated i.v. therapy with radiolabeled mouse monoclonal antibody (MAb) to carcinoembryonic antigen (CEA): 131I anti‐CEA was given approximately every 2 weeks with cyclosporin A, to suppress the anti‐mouse antibody response. Two schedules of cyclosporin A–intermittent therapy for 6 days with each course of anti‐CEA and continuous therapy–were compared. Suppression of the immune response in the intermittent high‐dose (3 patients) and continuous low‐dose groups (4 patients) was equivalent, but the latter regimen was less toxic. Repeated therapy led to the formation of small amounts of anti‐mouse antibody, but provided that cyclosporin A was continued it did not prevent further therapy or lead to an increase in the rate of clearance of anti‐CEA from blood. Without cyclosporin A no more than 2 courses of antibody therapy could be given. Patients received up to 4 doses of ml anti‐CEA. The nadir platelet count was related to the half‐life of 131I anti‐CEA in blood. Thrombocytopenia limited the amount of 131I anti‐CEA that could be given and determined the interval between treatments. Effective suppression of the anti‐antibody response is possible and this study has determined that myelosuppression is the principal obstacle to repeated therapy with radiolabeled antibody.