bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bispecific monoclonal antibody anti‐CD3 X anti‐tenascin: An immunotherapeutic agent for human glioma
Authors: Bonino Laura Davico , De Monte Lucia B. , Spagnoli Giulio C. , Vola Roberto , Mariani Massimo , Barone Domenico , Moro Ana M. , Riva Pietro , Nicotra Maria R. , Natali Pier Giorgio , Malavasi Fabio 
Published: February 2007

AbstractBesides surgery, the therapeutic possibilities for the treatment of human gliomas include adoptive cellular immuno‐therapy, radioimmunotherapy, immunotherapy mediated by chemoimmunoconjugates and, more recently, bispecific monoclonal antibodies (biMAbs). Anti‐CD3 x anti‐tenascin (TN) is the first reagent of a number of biMAbs under investigation for prospective use in vivo to maximize the cell‐mediated cytolytic potential of glioma patients. This biMAb originated from the fusion of 2 parental hybridomas, made resistant by retrovirus‐mediated infection to the different metabolic drugs, geneticin and methotrexate, respectively. The resulting hybrid hybridomas were selected on the basis of the double specificity for CD3 and TN, cloned several times and grown under continuous metabolic pressure. The different families of recombinant antibodies were then purified by high‐pressure liquid chromatography on hydroxylapatite columns. Immunohistochemical studies on tumor specimens of different origin and histotype have shown that the selected biMAb presented a distribution pattern similar to that of the parental anti‐TN MAb, maintaining the same staining homogeneity and intensity. Moreover, the mito‐genic activity of anti‐CD3 x anti‐TN biMAb on peripheral blood mononuclear cells was similar to that featured by the parental anti‐CD3 MAb. Furthermore, the hybrid molecule induced TNF‐α gene expression in activated PBMC. Finally, the anti‐CD3 x anti‐TN featured the desired killer targeting ability, being able to induce a significantly increased cytotoxic activity against TN† tumor cells. © 1995 Wiley‐Liss, Inc.
Selective inhibition of spontaneous pulmonary metastasis of lewis lung carcinoma by 5′‐deoxy‐5‐fluorouridine
Authors: Ishikawa Tohru , Ura Masako , Yamamoto Taeko , Tanaka Yutaka , Ishitsuka Hideo 
Published: February 2007

Abstract5′‐deoxy‐5‐fluorouridine (5′‐FUdR) is a cytostatic that is biotransformed to 5‐fluorouracil (5‐FUra) by pyrimidine nucleo‐side phosphorylase (PyNPase), the expression of which is up‐regulated by tumor necrosis factor α (TNFα), interleukin‐1 α (IL‐1α) and interferon γ (IFNγ). In Lewis lung carcinoma (LLC) cell cultures, these inflammatory cytokines up‐regulated the expression of type‐IV collagenase, a metastatic factor, as well as PyNPase and consequently enhanced the antiproliferative activity of 5′‐FUdR. However, the activity of 5‐FUra was not enhanced. It appears that 5′‐FUdR selectively kills highly metastatic cells which are exposed to these intrinsic cytokines in tumor tissues, because of their high PyNPase activity. In fact, 5′‐FUdR inhibited the spontaneous metastasis of LLC from the s.c. inoculation site to the lung. When 5′‐FUdR was given during the process of metastasis, it greatly reduced the number of tumor nodules in the lung even at doses 46 times lower than those inhibiting the primary tumor growth. In addition, 5′‐FUdR, but not 5‐FUra, lowered type‐IV collagenase levels in the tumors at the low dose showing only anti‐metastatic activity. On the other hand, 5‐FUra showed anti‐metastatic activity at doses similar to or only several times lower than those inhibiting the primary tumor growth. © 1995 Wiley‐Liss, Inc.
Expression of protectin (CD59) in human melanoma and its functional role in cell‐ and complement‐mediated cytotoxicity
Authors: Brasoveanu Lorelei I. , Altomonte Maresa , Gloghini Annunziata , Fonsatti Ester , Coral Sandra , Gasparollo Aldo , Montagner Roberto , Cattarossi Ilaria , Simonelli Cecilia , Cattelan Alessandro , Attadia Vincenza , Carbone Antonino , Malo Michele 
Published: February 2007

AbstractImmunohistochemical and/or indirect immunofluorescence analysis with monoclonal antibody (MAb) H19 demonstrated the expression of protectin (CD59) in 54 surgically removed metastatic melanoma lesions and on 8 out of 12 melanoma cell lines. CD59 expression had a low degree of intra‐ and intertumor heterogeneity. SDS‐PAGE analysis showed that the molecular weight of CD59 expressed on melanoma cells is about 20 kDa. Treatment of melanoma cells with 5 U/ml of phosphatidylinositol‐specific phospholipase C completely abolished cell‐surface expression of CD59. Interferon‐γ and/or tumor necrosis factor‐α or phorbol 12‐myristate 13‐acetate neither modulated the expression of CD59 by melanoma cells nor influenced the amounts of CD59‐specific mRNA. F(ab')2 fragments of anti‐CD59 MAb YTH53.1 did not inhibit the lysis of melanoma cells by allogeneic natural killer (NK) cells or lymphokine‐activated killer (LAK) cells. In contrast, the whole lg molecule of MAb H19 or YTH53. I significantly (p < 0.05) enhanced NK‐cell‐mediated lysis of melanoma cells, suggesting the induction of antibody‐dependent cell‐mediated cytotoxicity. Lastly, masking of CD59 by MAb YTH53. I or its F(ab')2 fragments significantly (p < 0.05) enhanced, in a dose‐dependent fashion, the lysis of anti‐GD3‐sensitized melanoma cells by homologous complement. These data demonstrate that CD59 expressed by human melanoma cells might regulate host‐tumor interaction by protecting neoplastic cells from complement‐mediated lysis. © 1995 Wiley‐Liss, Inc.
Quantitative and qualitative effects of experimental radioimmunotherapy on tumor vascular permeability
Authors: Blumenthal Rosalyn D. , Kashi Rina , Sharkey Robert M. , Goldenberg David M. 
Published: February 2007

AbstractLocalization of radiolabeled antibodies in the perivascular space of tumors resulted in morphological changes in blood vessel structure and physiological changes in tumor vessel function. Vessel diameter decreased by day 14 and was associated with a significant decline in vascular volume (VV). Upon recovery of VV, the basement membrane surrounding the endothelium had thickened. Tumor vascular permeability (VP) decreased within 7 days of treatment and remained suppressed throughout the 42‐day observation period of our study. The decline in VP, which could be visualized by fluorescent microscopy of FITC‐dextran extravasation, was dose‐related and could be quantified at doses as low as 800 cGy. The radioantibody‐induced 50–80% decline in tumor VP was observed in 3 human colonic xenografts (GW‐39, LS174T and MOSER). Decreases in VP have been observed for proteins ranging in size from 20 to 150 kDa. Similar effects on VP were noted when low protein doses (10–30 μg), which resulted in heterogeneous antibody distribution, were used or with high protein doses (400–750 μg), which resulted in more uniform penetration of antibody. If 188Re or 90Y, radiometals with higher β‐energy and longer path lengths, were substituted for 131I, a similar decrease in VP was observed. The radioimmunotherapy (RAIT)‐induced decrease in tumor VP resulted in a 90% decline in accretion of a second dose of radioantibody. The 10% of the second dose that was taken up by the tumor targeted many already non‐viable tumor regions and some, but not all, viable tumor cell clusters. © 1995 Wiley‐Liss, Inc.
Calibration of misonidazole labeling by simultaneous measurement of oxygen tension and labeling density in multicellular spheroids
Authors: Gross Markus W. , Karbach Ulrich , Groebe Karlfried , Franko Allan J. , Mueller‐Klieser Wolfgang 
Published: February 2007

AbstractTo correlate misonidazole concentrations and oxygen pressures (Po2) at identical locations within EMT6/Ro multi‐cell spheroids (mean diameters ± SD: 867 ± 20 μm), Po2 measurements were performed with oxygen‐sensitive microelectrodes during incubation of these spheroids with tritiated misonidazole (10 mg/l; 445 μCi/mg). In each individual spheroid, Po2 profiles were correlated with the corresponding spatial distribution of misonidazole as quantified by conventional autoradiography and grain counting. To compare the oxygenation status of spheroids in the measuring chamber with that of spheroids in spinner culture, misonidazole labeling was performed in both environments following the same protocol. All experiments were conducted in 20% oxygen and BME or in 5% oxygen and DMEM to obtain spheroids with different degrees of oxygenation. Labeled misonidazole was fairly evenly distributed in the outer, better oxygenated regions of EMT6 spheroids. In contrast, there was an accumulation of the labeled substance near central necrosis where low oxygen tensions were measured. Grain densities were similar at corresponding oxygen pressures under both environmental conditions. Except for some scatter, grain density as a function of oxygen pressure showed little variation in the Po2 range of 20–60 mm Hg, but exhibited a steep increase below 10 mm Hg. The findings imply that a substantial rise in local misonidazole labeling indicates a meta‐bolically active tissue region at low Po2 that is not necessarily identical with the radiobiologically hypoxic cell fraction. A comparison of the labeling densities of spheroids in spinner flasks and in the Po2 measuring chamber indicates that oxygenation of spheroids is better in rotation culture than during microelectrode measurements. © 1995 Wiley‐Liss, Inc.
B‐cell lymphomagenesis in SIV‐immunosuppressed cynomolgus monkeys
Authors: Rezikyan Susanna , Kaaya Ephata E. , Ekman Marianne , Voevodin Alexander F. , Feichtinger Hans , Putkonen Per , Castaños‐Velez Esmeralda , Biberfeld Gunnel , Biberfeld Peter 
Published: February 2007

AbstractB‐cell lymphomas developed frequently (approx. 40%) in SIVsm (SMM3) immunosuppressed monkeys and were mostly extranodal, aggressive and all associated with an EBV‐related simian herpes virus operationally designated herpes virus Macoca fascicularis (HVMF‐1). Lymphoma tissues from 21 monkeys were studied by PCR and DNA PAGE for mono/oligoclonality of the VDJ‐rearranged IgH genes. Most lymphomas (n = 15) showed a monoclonal and approximately 1/3 (n = 6) an oligoclonal VDJ rearrangement pattern. The time after infection to tumor presentation was significantly shorter for oligoclonal than for monoclonal lymphomas, suggesting that oligoclonal selection frequently precedes the outgrowth of a single malignant clone. Comparison of the VDJ rearrangements in an established lymphoma cell line and the original, oligoclonal lymphoma tissue indicated in vitro selection of one HVMF‐infected clone. Longitudinal studies of sequential lymph‐node biopsies showed that the malignant lymphoma clone in 3 out of 8 lymphomas could be identified as a predominant clone in lymph nodes 2‐12 months after SIV infection and 6‐10 months before clinical presentation of the lymphomas. VDJ‐rearranged DNA corresponding to that of the lymphomas was also detected in most sera at the time of lymphoma manifestation but not in corresponding PBL preparations. Clearly, the SIVsm AIDS model in cynomolgus monkeys represents a powerful tool for biological and clinical studies of herpes‐virus‐associated lymphomagenesis in immunosuppressed states. © 1995 Wiley‐Liss, Inc.
International renal‐cell cancer study. IV. Occupation
Authors: Mandel Jack S. , McLaughlin Joseph K. , Schlehofer Brigitte , Mellemgaard Anders , Helmert Uwe , Lindblad Per , McCredie Margaret , Adami Hans‐Olov 
Published: February 2007

AbstractThe relationship between renal‐cell cancer (RCC) and occupation was investigated in an international multicenter population‐based case‐control study. Study centers in Australia, Denmark, Germany, Sweden and the United States interviewed 1732 incident RCC cases and 2309 controls. Significant associations were found with employment in the blast‐furnace or the coke‐oven industry [relative risk (RR), 1.7; 95% confidence interval (CI), 1.1–2.7], the iron and steel industry (RR, 1.6; 95% CI, 1.2–2.2) and exposure to asbestos (RR, 1.4; 95% CI, 1.1–1.8), cadmium (RR, 2.0; 95% CI, 1.0–3.9), dry‐cleaning solvents (RR, 1.4; 95% CI, 1.1–1.7), gasoline (RR, 1.6; 95% CI, 1.2–2.0) and other petroleum products (RR, 1.6; 95% CI, 1.3–2.1). Asbestos, petroleum products and dry‐cleaning solvents appear to merit further investigation, in view of the relationship between risk and duration of employment or exposure and after adjustment for confounding. There was a negative association between RCC and education, but it was not consistent across all centers. Overall, the results of our multicenter case‐control study suggest that occupation may be more important in the etiology of RCC than indicated by earlier studies. © 1995 Wiley‐Liss, Inc.
Is residence in areas of endemic goiter a risk factor for thyroid cancer?
Authors: Galanti Maria Rosaria , Sparén PÄR , Karlsson Anders , Grimelius Lars , Ekbom Anders 
Published: February 2007

AbstractThe association between an indicator of iodine deficiency and differentiated thyroid cancer has been investigated in a population‐based case‐control study. This included all incident cases (N = 484) of papillary and follicular thyroid cancer diagnosed during the years 1980–1992 in a Swedish Health Care Region among residents born in Sweden, and as many individually matched controls. Cases were included after a uniform review of their histopathological specimens. Residence in areas where goiter had been severely endemic in the 1930s was used as exposure indicator. Odds ratios (OR) and 95% confidence intervals as estimates of relative risk were calculated as a measure of association using logistic regression. A trend toward an association was found with a duration of residence in goiter areas between 21 and 40 years, most prominent among follicular cancer cases and in the group diagnosed at age ≶ 50 years compared to not exposed. Exposure for the first time during adolescence (between 11 and 20 years) was associated with an increased risk of papillary cancer. This was especially evident among women, both when compared to not exposed and to those exposed during the first year of life; the association was strengthened after adjustment for duration of residence. These findings support the hypothesis of distinct causation patterns from iodine deficiency to the 2 most common histological types of thyroid cancer. © 1995 Wiley‐Liss, Inc.
Time trend in pancreatic cancer incidence in connecticut, 1935–1990
Authors: Zheng Tongzhang , Holford Theodore R. , Ward Barbara A. , McKay Lisa , Flannery John , Boyle Peter 
Published: February 2007

AbstractA total of 13,246 incident pancreatic cancer cases, reported to the Connecticut Tumor Registry between 1935 and 1990, were included in our study. Results indicate that the overall age‐adjusted incidence rate of pancreatic cancer increased between 1935 and 1964 in males, and leveled off thereafter. Since 1975, the incidence rate has in fact been decreasing, from 12.04/100,000 in 1975–79 to 10.44/100,000 in 1985–90. In females, the overall age‐adjusted incidence rate also increased between 1935 and 1974. Since then, however, it has remained relatively stable. Age‐specific incidence rates also show no signs of an increase in rate from any age group, or from either sex for recent birth cohorts. There is also no clear increase in the incidence of pancreatic cancer in any of the ethnic/gender categories since the early 1970s. Age‐period‐cohort modeling shows that the increasing birth cohort trend peaked among those born around 1920–1925 and, for recent birth cohort, a slightly decreasing trend was observed in both males and females. Our study reveals no signs of an increase in the immediate future in pancreatic cancer incidence rate in any of the sex, ethnic and age groups in Connecticut. © 1995 Wiley‐Liss, Inc.
Mechanism of interaction between cisplatin and human recombinant interferon gamma in human ovarian‐cancer cell lines
Authors: Nehmé Alissar , Albin Nicolas , Caliaro Marie Josée , Guichard Sylvie , Jozan Suzanne , Julia Anne‐Marie , Bugat Roland , Canal Pierre 
Published: February 2007

AbstractHuman ovarian carcinoma cells (2008 and its cisplatin‐resistant sub‐line 2008/C13*) were sensitized to cisplatin by treatment with human recombinant gamma interferon (IFNγ). IFNγ produced no significant change in the uptake of CDDP. Exposure of 2008 and 2008/C13* cells to IFNγ resulted in a time‐dependent decrease of cellular glutathione and total glutathione‐S‐transferase activity, principally the π isoform. By contrast, the treatment of 2008 and 2008/C13* cell lines with IFNγ induced rather than suppressed metallothionein IIA mRNA levels. IFNγ changed neither the formation of total platinum‐DNA adducts, nor DNA repair. A significant decrease in c‐erbB‐2 expression was observed both in sensitive and in resistant cell lines after treatment with IFNγ, and this decrease was dose‐dependent. Our results indicate that the mechanism of IFNγ‐induced sensitization in human ovarian‐cancer cell lines is multifactorial. © 1995 Wiley‐Liss, Inc.
RB‐reconstituted human retinoblastoma cells form RB‐positive intraocular and intracerebral but not subcutaneous tumors in scid mice
Authors: Szekely Laszlo , Wang Yisong , Klein George , Wiman Klas G. 
Published: February 2007

AbstractWERI‐Rb 27 human retinoblastoma cells were reconstituted with an intact RB gene by retrovirus‐mediated gene transfer, in order to study the phenotypic effects of the protein in vitro and in vivo. Extensive morphological changes were observed, dominated by the formation of multinucleated giant cells. Six weeks after retroviral infection, the giant cells began to die and small cells emerged, resembling the parental non‐reconstituted line. They expressed RB and continued to grow, although they showed an increased sensitivity to serum starvation. The original RB‐negative cells grew progressively after subcutaneous inoculation into SCID mice, whereas the reconstituted cells failed to grow. RB‐positive cells grew progressively in the corpus vitreum of the eye and in the brain, however. The RB‐reconstituted cells grew more slowly and were less invasive than the parental cells and cells infected with a firefly luciferase (LUX) gene carrying retrovirus, used as controls. RB‐reconstituted cells re‐explanted from the intraocular and intracranial tumors continued to express full‐length RB protein. RBeye2, an RB‐positive cell line established from an eye tumor, was still unable to grow subcutaneously. The reduced tumorigenicity of the RB‐reconstituted cells in the subcutaneous space may be due to the influence of locally acting growth‐controlling signals or the absence of microenvironment‐specific trophic factors. Alternatively, it may reflect the action of residual immune effectors in the SCID mice. If this is the case, these would have to be more effective at the subcutaneous site than in the eye or brain. © 1995 Wiley‐Liss, Inc.
Alterations in the signal‐transducing molecules of T cells and nk cells in colorectal tumor‐infiltrating, gut mucosal and peripheral lymphocytes: Correlation with the stage of the disease
Authors: Matsuda Masanori , Petersson Max , Lenkei Rodica , Taupin Jean‐Luc , Magnusson Inger , Mellstedt Håkan , Anderson Paul , Kiessling Rolf 
Published: February 2007

AbstractT cells from mice bearing an experimental colon carcinoma, and from patients with colorectal and renal carcinomas, have atypical T‐cell receptors (TCR). In the present study, further characterization of modulations in CD3‐ and CD 16‐associated ζ chain in peripheral blood lymphocytes (PBL) and tumor‐infiltrating lymphocytes (TIL) from colorectal carcinomas was performed. Relative to PBL, the percentage of natural killer (NK) cells among fresh TIL was reduced, while a higher proportion of T cells expressing HLA‐DR was found. As previously reported, we found significantly reduced levels of the CD3‐ and CD 16‐associated ζ chain in TIL and, to a lesser extent, also in patients' PBL. Levels of ζ chain in T and NK cells from non‐cancerous colorectal tissue from patients were lower than in PBL but higher than in TIL, with a direct relationship between levels of this signal‐transducing molecule and the distance from the tumor. In addition, ζ levels correlated with the Dukes' stage of the disease, since PBL from patients with lymph‐node involvement or distant organ metastases (Dukes' stages C and D) had significantly less CD3 ζ than patients with localized disease (stages A and B). Patients' T cells also had decreased levels of cell‐surface and cytoplasmic CD3 ϵ. We also observed reduced levels of the TCR accessory molecules CD4 and CD8, mainly on TIL but to a lesser extent also on patients' PBL. Biochemical analysis of anti‐CD3 ϵ‐immunoprecipitated TCR complexes demonstrated that the CD3 complex was not associated with the ζ chain, either on TIL or on PBL or on lymphocytes from non‐cancerous colon tissue, suggesting a defect in the assembly of the TCR complex. Following several days of in vitro culture with recombinant interleukin‐2 and phytohemagglutinin, anti‐CD3 or anti‐CD2 monoclonal antibodies (MAbs), levels of CD3 ζ chain as well as of cell surface CD3 ϵ were normalized. Our findings suggest an abnormal expression as well as assembly of several different signal‐transducing molecules of T cells and NK cells, which correlate with the stage of the disease in patients with colorectal carcinomas. © 1995 Wiley‐Liss, Inc.
Risks of second primary malignancy in patients with cutaneous and ocular melanoma in denmark, 1943–1989
Authors: Swerdlow A. J. , Storm H. H. , Sasieni P. D. 
Published: February 2007

AbstractRisks of 2nd primary cancer were assessed in all patients with cutaneous melanoma (12,460) and all patients with ocular melanoma (2,018) incident in Denmark from 1943 to 1989 and followed for totals of 88,667 person‐years and 16,045 person‐years, respectively. After cutaneous melanoma, 972 2nd cancers occurred. The risk of non‐melanoma skin cancer was significantly raised in each sex. Risk of all non‐skin cancers was not raised for all ages but was significantly increased for patients with the primary melanoma incident at ages under 50 years (standardised incidence ratio [SIR], i.e., ratio of observed to expected cancer incidence, multiplied by 100 = 117; 95% confidence interval [CI] 101 – 134). There were significantly increased risks of chronic lymphocytic leukaemia in males and both sexes combined, brain and nervous system cancers in females and both sexes combined and oropharyngeal cancer in both sexes combined. Risk of pancreatic cancer was not raised, suggesting that cutaneous melanoma patients generally do not share the diathesis for this malignancy which has been observed in certain families with atypical naevi and melanoma. There was no relation of 2nd primary cancer risks to duration since the first primary and no indication of any appreciable treatment‐related risk. After ocular melanoma, 216 2nd cancers occurred. There was a significantly increased risk of 2nd cancer overall in males but not females and a significantly increased risk of liver cancer in each sex. Risk of non‐melanoma skin cancer (NMSC) was not raised, which suggests that the aetiology of ocular melanoma is not mainly dependent on UV exposure, at least of the type causing NMSC. © 1995 Wiley‐Liss, Inc.