bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific immunotherapy against occult cancer metastases
Authors: Lu Weixin , Dong Zhongyun , Donawho Cherrie , Fidler Isaiah J. 
Published: September 2002

AbstractWe investigated the efficacy of a preparation containing High Five (H5) insect cells infected with recombinant baculovirus encoding the murine interferon‐β gene (H5BVIFN‐β) against established primary tumors and occult lung metastases. Injection of live or lyophilized H5BVIFN‐β into established subcutaneous tumors of the highly metastatic murine UV‐2237m fibrosarcoma or K‐1735M2 melanoma in syngeneic mice eradicated both primary tumors and preexisting lung metastases. The therapeutic effects of H5BVIFN‐β were not observed in nude mice and were diminished in syngeneic mice depleted of CD4+ and CD8+ T cells. Immunohistochemical staining showed that tumors injected with H5BVIFN‐β were densely infiltrated by CD4+ and CD8+ T cells in mice with normal CD4/CD8 complement. These data demonstrate that, unlike most immunologic approaches in which prophylaxis can be achieved but eradication of established tumor is rare, lyophilized preparations of H5BVIFN‐β can serve as a novel immunotherapy against both primary tumors and their occult metastases. © 2002 Wiley‐Liss, Inc.
Metabolism and DNA binding of the environmental pollutant 6‐nitrochrysene in primary culture of human breast cells and in cultured MCF‐10A, MCF‐7 and MDA‐MB‐435s cell lines
Authors: Boyiri Telih , Leszczynska Joanna , Desai Dhimant , Amin Shantu , Nixon Daniel W. , El‐Bayoumy Karam 
Published: September 2002

AbstractThe environmental pollutant 6‐nitrochrysene (6‐NC) is a potent mammary carcinogen in the rat. To determine if the results obtained in 6‐NC‐treated rodents can be applicable to humans, we examined its metabolic activation in primary cultures of human breast cells prepared from tissues obtained from reduction mammoplasty from 3 women and in a cultured, immortalized human mammary epithelial cell line (MCF‐10A), as well as estrogen‐dependent (MCF‐7) and estrogen‐independent (MDA‐MB‐435s) human breast cancer cell lines. Metabolites identified following 24 hr incubations of [3H]6‐NC (2.5, 5.0 and 10 μM) with human breast cells were derived from ring‐oxidation (trans‐1,2‐dihydroxy‐1,2‐dihydro‐6‐nitrochrysene [1,2‐DHD‐6‐NC]) and nitro‐reduction (6‐aminochrysene [6‐AC]); chrysene‐5,6‐quinone (C‐5,6‐Q) was also detected. Levels of metabolites (pmol/mg protein) varied greatly depending on the concentration of 6‐NC and the individual breast tissue used; 1,2‐DHD‐6‐NC, ranged from not detected to 15.6 ± 1.0; 6‐AC, from 11.5 ± 4.0 to 155 ± 10.2; C‐5,6‐Q, from 18.3 ± 10.8 to 196.7 ± 15.4. Qualitatively similar metabolic profiles were obtained upon incubation of [3H]6‐NC with MCF‐10A, MCF‐7 and MDA‐MB‐435s. We also detected 1,2‐dihydroxy‐6‐aminochrysene (1,2‐DH‐6‐AC; ranged from not detected to 50.4 ± 9.8). Some of the metabolites identified in our study are known to be proximate carcinogenic forms of 6‐NC in rodents. MCF‐7 was the most efficient cell line in catalyzing 6‐NC to genotoxic metabolites, and we demonstrated that the major DNA adduct is chromatographically identical to that found in the mammary gland of rats treated by gavage with 6‐NC and that obtained from the incubation of [3H]1,2‐DHD‐6‐NC with MCF7 cells or from nitro‐reduction of 1,2‐DHD‐6‐NC in the presence of 2′‐deoxyguanosine 5′‐monophosphate in vitro. This is the first report to demonstrate the ability of human breast cells, MCF‐10A, and breast cancer cell lines to activate 6‐NC to metabolites that can damage DNA. © 2002 Wiley‐Liss, Inc.
Development of HLA‐A2402/Kb transgenic mice
Authors: Gotoh Masashi , Takasu Hideo , Harada Kenji , Yamaoka Takashi 
Published: September 2002

AbstractHLA‐transgenic mice have been developed to facilitate studies of HLA‐restricted cytotoxic responses, e.g., for the identification of immunodominant HLA‐restricted CTL epitopes and the optimization of peptide or DNA vaccine constructs for human use. We have developed HLA‐A2402/Kb‐transgenic mice expressing chimeric human (α1 and α2 domains of HLA‐A2402) and mouse (α3, transmembrane and cytoplasmic domains of H‐2Kb) class I molecules. Immunization of these HLA‐A2402/Kb‐transgenic mice with various known HLA‐A24‐restricted immunodominant cancer CTL epitope peptides derived from gp100, MAGE‐1, MAGE‐3, Her2/neu, CEA and TERT induced HLA‐A24‐restricted, peptide‐specific CTLs. Using these transgenic mice, we identified a novel HLA‐A24‐restricted CTL epitope, PSA152–160, encoded by human prostate‐specific antigen. Staining with HLA tetramers showed that the cytotoxic activity induced by immunizing with PSA152–160 in HLA‐A2402/Kb transgenic mice was HLA‐A2402‐restricted and CD8‐dependent. Therefore, PSA152–160 might be a candidate peptide for vaccination of HLA‐A24+ patients with prostate cancer. Our results suggest that HLA‐A2402/Kb transgenic mice might be useful in the search for HLA‐A24‐restricted CTL epitopes functioning as human cancer antigens and for the development of peptide‐based cancer immunotherapy. © 2002 Wiley‐Liss, Inc.
Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas
Authors: Moon Nam Sung , Rong Zeng Wendy , Premdas Peter , Santaguida Marianne , Bérubé Ginette , Nepveu Alain 
Published: September 2002

AbstractGenetic analyses and mRNA expression studies have implicated CUTL1 as a candidate tumor‐suppressor gene in uterine leiomyomas and breast cancers. However, modulation of CDP/Cux, the protein encoded by CUTL1, does not agree with this notion. The activity of CDP/Cux, which is the DNA binding subunit of HiNF‐D, was upregulated as normal cells progressed into S phase and constitutively elevated in several tumor cell lines. Activation of CDP/Cux at the G1/S transition involved the proteolytic processing of the protein to generate a shorter isoform. Uterine leiomyomas represent a unique reagent for molecular analysis because they are resected as homogenous tumor tissue together with the adjacent normal myometrium and they are often very large. In the present study, proteins were isolated from 16 pairs of matched tumors and adjacent myometrium and analyzed by Western blot and electrophoretic mobility shift assays. Strikingly, in 11/16 tumors, the steady‐state level of small CDP/Cux isoforms was increased compared to normal control tissue. Where tested, a corresponding increase in CDP/Cux stable DNA binding activity was observed. DNA sequencing analysis of CUTL1 cDNAs from 6 leiomyomas, including 4 with LOH of CUTL1, did not reveal any gross rearrangement or point mutations. Altogether these findings suggest that CUTL1 is probably not the tumor suppressor on 7q22. Moreover, the frequent increase in smaller CDP/Cux isoforms indicates that molecular events associated with the truncation of CDP/Cux proteins may be selected in uterine leiomyomas. © 2002 Wiley‐Liss, Inc.
A population‐based familial aggregation analysis indicates genetic contribution in a majority of renal cell carcinomas
Authors: Gudbjartsson Tómas , Jónasdóttir Thora J. , Thoroddsen Ásgeir , Einarsson Gudmundur V. , Jónsdóttir Gudrún M. , Kristjánsson Kristleifur , Hardarson Sverrir , Magnússon Kjartan , Gulcher Jeffrey , Stefánsson Kári , Ámundadóttir Laufey T. 
Published: September 2002

AbstractThe etiology of RCC is incompletely understood and the inherited genetic contribution uncertain. Although there are rare mendelian forms of RCC stemming from inherited mutations, most cases are thought to be sporadic. We sought to determine the extent of familial aggregation among Icelandic RCC patients in general. Medical and pathologic records for all patients diagnosed with RCC in Iceland between 1955 and 1999 were reviewed. This included a total of 1,078 RCC cases, 660 males and 418 females. With the use of an extensive computerized database containing genealogic information on 630,000 people in Iceland during the past 11 centuries, several analyses were conducted to determine whether the patients were more related to each other than members drawn at random from the population. Patients with RCC were significantly more related to each other than were subjects in matched groups of controls. This relatedness extended beyond the nuclear family. RRs were significantly greater than 1.0 for siblings, parents and cousins of probands. RRs were 2–3 for first‐degree relatives and 1.6 for third‐degree relatives. The risk of RCC is significantly higher for members of the extended family of an affected individual, as well as the nuclear family. Our results indicate that germline mutations are significantly involved in what has been defined as sporadic RCC. © 2002 Wiley‐Liss, Inc.
ICAM‐1 expression and the soluble ICAM‐1 level for evaluating the metastatic potential of gastric cancer
Authors: Maruo Yukinobu , Gochi Akira , Kaihara Akihiko , Shimamura Hiroshi , Yamada Takatoshi , Tanaka Noriaki , Orita Kunzo 
Published: September 2002

AbstractICAM‐1 plays an important role in cell–cell and cell–extracellular matrix interactions, especially tumor invasion and cytotoxicity of lymphocytes. In the present study, the relationship between metastasis of gastric cancer and ICAM‐1 expression by cancer cells or the serum level of s‐ICAM‐1 was (s‐ICAM‐1) was examined. ICAM‐1 was detected by immunohistochemic staining in 49.0% of 108 patients with gastric cancer. The ICAM‐1 expression rate was higher at a more advanced stage, based on lymph node metastasis, being 46.9% in node‐negative and 56.1% in node‐positive cases. In patients with liver metastasis, the rate was 90.9%, while it was 43.3% in patients without liver metastasis (p < 0.05). The serum s‐ICAM‐1 level was 262.1 ng/ml (median 205.5, range 176.0–271.0) in healthy subjects and 391.5 ng/ml (median 317.5, range 148.7–1,768.0) in gastric cancer patients (p < 0.001). The serum s‐ICAM‐1 level was significantly higher in patients with liver metastasis than in patients without liver metastasis (p < 0.0001). In addition, positive ICAM‐1 expression cases had significantly higher s‐ICAM‐1 levels than negative ones, 408.9 ± 188.4 and 308.1 ± 88.1 ng/ml, respectively. These results suggested that ICAM‐1 was overexpressed in cancer cells and released as s‐ICAM‐1, which would promote hematogenous metastasis by suppressing local anticancer immunity. © 2002 Wiley‐Liss, Inc.
Inflammation and cancer, the mastocytoma P815 tumor model revisited: Triggering of macrophage activation in vivo with pro‐tumorigenic consequences
Authors: Kamate Caroline , Baloul Samia , Grootenboer Sabine , Pessis Eric , Chevrot Alain , Tulliez Micheline , Marchiol Carmen , Viguier Mireille , Fradelizi Didier 
Published: September 2002

AbstractSubcutaneous in vivo injections of cells of the mastocytoma line P815 in syngenic DBA/2 mice induce locally fast growing solid tumors. These have been used extensively as a cancer model to analyze and manipulate the relationship between tumor cells and host's immune defenses. We report that progression of P815 tumors in vivo was accompanied by a burst (Days 5–7) of local inflammatory cells recruitment and angiogenesis observed histologically, corroborated in vivo by MRI with gadolinium, overtranscription of macrophage activation marker genes, secretion of TNF‐α by regional lymph node cells and concomitant systemic inflammation. No substantial overtranscriptions of either VEGF or IL‐10 or TGF‐β genes were observed. Induction of COX‐2 gene was a late event. To establish a possible relationship between the tumor‐induced local, regional and systemic increase of pro‐inflammatory mediators and progression of tumors in vivo, we carried out experiments deliberately modulating the inflammatory status of the recipient animals. Pretreatment of recipient animals by i.p. injection of thioglycolate accelerated P815 tumor growth. At the opposite, treatment of mice with either a COX‐1 + COX‐2 inhibitor (aspirin, 1 mg/day/mouse) or a specific COX‐2 inhibitor (celecoxib, 0.13 mg/day/mouse) for 2 weeks after injection of tumor cells, significantly reduced the size and growth rate of tumors compared to control mice. Experiments carried out in vitro indicated that peritoneal macrophages from untreated animals were strongly activated by live P815 cells and by P815 membrane preparations. The tumor‐induced inflammatory reaction could establish a local micro environment favoring tumor progression. The P815 tumor model might be helpful to recognize important factors controlling host/tumor relationship. © 2002 Wiley‐Liss, Inc.
Progenipoietin‐generated dendritic cells exhibit anti‐tumor efficacy in a therapeutic murine tumor model
Authors: Björck Pia , Lie Wen‐Rong , Woulfe Susan L. , Klein Barbara K. , Olson Walter , Storkus Walter J. 
Published: September 2002

AbstractProgenipoietin (ProGP‐4) is a chimeric molecule, exhibiting both Flt‐3 and granulocyte‐colony stimulating factor (G‐CSF) receptor agonist activities. Subcutaneous administration of ProGP‐4 to BALB/c mice at a dose of 40–100 μg/day for up to 12 consecutive days induces both CD11c+ dendritic cells (DCs) and CD11c−/CD11b+ granulocytes in spleen, blood and lymph nodes of treated animals. Peak numbers of all cell populations were observed on day 7 of treatment, with CD11c+ DCs representing approximately 8% of total splenocytes at that time. Approximately 40–50% of these CD11c+ cells were also able to endocytose and process the exogenous fluorescent antigen DQ‐BSA. As a test of their therapeutic utility, freshly prepared CD11c+ DCs were pulsed with a defined tumor‐associated peptide epitope (murine p53232–240) and injected as a vaccine into BALB/c mice bearing day 7 established CMS4 sarcomas. Similarly prepared DCs were injected again 1 week later. Based on our results, we conclude that (i) both peptide‐pulsed CD11c+ DCs (harvested directly from ProGP‐4 treated mice) and pulsed bone marrow‐derived DCs effectively slow the growth of or mediate the regression (in 25 of 89 [28%] cases) of CMS4 tumors, and (ii) nonpulsed DCs mediated minimal or no therapeutic effect. These data support the ability of ProGP‐4 to enhance the peripheral frequencies of DCs that exhibit therapeutic efficacy when applied as a vaccine to treat tumor‐bearing animals. © 2002 Wiley‐Liss, Inc.
Concordance of allelic imbalance profiles in synchronous and metachronous bilateral breast carcinomas
Authors: Imyanitov Evgeny N. , Suspitsin Evgeny N. , Grigoriev Maxim Yu. , Togo Alexandr V. , Kuligina Ekatherina Sh. , Belogubova Evgeniya V. , Pozharisski Kazymir M. , Turkevich Elena A. , Rodriquez Carmen , Cornelisse Cees J. , Hanson Kaido P. , Theillet Charles 
Published: September 2002

AbstractBilateral breast cancer (biBC) is a common form of breast cancer; however, it has not been subjected to systematic comparative genetic studies. We allelotyped 28 biBCs on 14 chromosomal arms, addressing 2 lines of questions: (i) does comparison of genetic profiles disclose contralateral metastases misdiagnosed as second primaries? and (ii) do shared environmental and host factors drive the development of true biBC along similar genetic routes? Allelotyping provided unambiguous proof for distinct clonality in 23 of 28 cases. In another 4 biBCs, the genotyping data did not exclude the hypothesis of metastatic spread, whereas clinical and histologic data were in favor of bilaterality. Thus the question of clonality remained open only for 1 case, in which the paired tumors shared both histologic features and allelotypes. We conclude that the vast majority if not all biBCs are of independent clonal origin. Next, we assessed the similarity of genetic pathways in distinct categories of biBC. It was assumed that the coexistence of allelic imbalance (AI) in 1 tumor and retention of heterozygosity (N) in the contralateral neoplasm corresponds to the distinct genetic profiles, whereas the remaining combinations (AI/AI or N/N) suggest a match of allelic status for a given polymorphic marker. When these allelic matches were pooled, it turned out that synchronous biBC displayed a significantly higher similarity score than metachronous biBC (64/77 [83%] vs. 162/267 [61%]; p = 0.0003). In addition, an increased similarity of allelic profiles was observed in the premenopausal biBC (76/101 [75%]) compared with postmenopausal cases (111/173 [64%]) or tumor pairs separated by the onset of menopause (39/70 [56%]; p = 0.014). Overall, our data suggest that sharing natural histories of the disease, which is more evident in synchronous and/or premenopausal forms of biBC, may result in a similarity of molecular portraits in bilateral breast tumors. © 2002 Wiley‐Liss, Inc.
A synthetic matrix metalloproteinase inhibitor prevents squamous carcinoma cell proliferation by interfering with epidermal growth factor receptor autocrine loops
Authors: O‐Charoenrat Pornchai , Rhys‐Evans Peter , Eccles Suzanne 
Published: September 2002

AbstractHead and neck squamous cell carcinoma (HNSCC) is characterized by its capacity to invade adjacent tissues and to metastasize locoregionally. Evidence suggests that matrix metalloproteinases (MMPs) may play a causal role in HNSCC progression. While evaluating the role of MMPs in the invasion process, we made the surprising observation that a broad‐spectrum MMP inhibitor, (marimastat, BB2516), inhibited the growth in vitro of some HNSCC cell lines. This inhibitory effect was only found in HNSCC cell lines overexpressing epidermal growth factor receptors. The effects of the MMP inhibitor could be reversed by adding exogenous c‐erbB ligands, suggesting that the phenomenon may be related to autocrine ligand processing. This hypothesis was supported by the finding that the growth‐inhibitory effect of marimastat was directly related to its ability to prevent the release of major c‐erbB ligands including transforming growth factor‐α, betacellulin and heregulin β1 from HNSCC. Marimastat was also found to potentiate the cytotoxic effects of cisplatin both in vitro and in vivo. Our results indicate that the cleavage of several c‐erbB ligands from membrane‐anchored precursors requires MMP activity. We conclude that MMP inhibitors could prevent tumor progression not only by inhibiting invasion and angiogenesis, as previously shown, but also by their ability to inhibit autocrine signaling through the c‐erbB receptors. Clinical trials to test this hypothesis in HNSCC should be considered. © 2002 Wiley‐Liss, Inc.
Etude comparative de la disponibilité de l'eau en irrigation goutte à goutte
Authors: Ould Mohamed El‐Hafedh A.V. , Daghari H. , Maalej M. 
Published: September 2002

AbstractDans le but de déterminer la meilleure combinaison entre période et durée d'irrigation pour différents écartements inter‐goutteurs, nous avons essayé d'analyser la disponibilité de l'eau au sein de la zone racinaire d'une culture de tomate irriguée à l'aide d'une rampe de goutteurs débitant chacun 4 l h−1. Trois écartements ont été étudiés à savoir 30, 50 et 70 cm.Lorsqu'on a pris une durée d'arrosage systématique de 4h30mn, nous avons observé à la fin des irrigations des teneurs en eau volumiques moyennes dépassant la capacité au champ pour les trois écartements. En effet, à l'examen de l'évolution des teneurs en eau au sein du bulbe, il est remarqué que la teneur en eau à la capacité au champ a été atteinte après 25 minutes, 50 minutes et deux heures respectivement pour 30, 50 et 70 cm. Mais l'humidification de toute la ligne de culture n'a été observée qu'après des temps respectifs d'une heure, deux heures et quatre heures (Ould Mohamed El‐Hafedh et al., 2000).Les irrigations ont été reprises avec ces durées réduites (une heure, deux heures et quatre heures respectivement pour les écartements 30, 50 et 70 cm) en vue d'évaluer et comparer les consommations en eau de la culture sous les différents traitements.Dans le cas de l'irrigation d'une durée de 4h30mn, la période séparant deux arrosages successifs a été de cinq, quatre et trois jours respectivement pour les écartements 30, 50 et 70 cm. Pour les irrigations des durées réduites, on a constaté qu'il est impératif d'irriguer après trois jours pour les deux écartements 50 et 70 cm et après deux jours pour l'écartement 30 cm.En comparant les consommations en eau pour les durées réduites et la durée systématique de 4h30mn, on a observé une économie d'eau de l'ordre de 20, 15 et 5% respectivement pour 30, 50 et 70 cm d'écartement. D'autre part, la comparaison entre les durées réduites montre que la plus importante économie en eau a été réalisée avec 50 cm d'écartement. Copyright © 2001 John Wiley & Sons, Ltd.
Conjunctive use of surface and groundwater: overview and perspective
Authors: de Wrachien Daniele , Fasso Costantino A. 
Published: September 2002

AbstractThe world's fresh water resources are unequally distributed both in time and in space. Until recently water resource management focused on reallocating water to when and where it was required, a supply‐side or fragmented approach. Nowadays there are signs that water resource availability is dwindling—due to both population growth and increased per capita water use—and ecosystems are being damaged. To face this challenge a new holistic approach is needed. This approach includes the integrated or conjunctive use of surface and groundwater resources and takes account of social, economic and environmental factors. Moreover, it recognizes the importance of water quality issues.In this context, the paper examines the main aspects and problems concerned with the planning, design, construction and management of conjunctive use of surface and subsurface water resources, along with its environmental impacts and constraints to sustainable development. The importance and role of research thrust, technology transfer, institutional strengthening, effective partnerships between governments and stakeholders, and sound financial frameworks are also examined. Finally, the challenges and benchmarks for future actions that the scientific community and planners have to face and deal with, are briefly outlined. Copyright © 2002 John Wiley & Sons, Ltd.
Stability and wage acceleration in macroeconomic models of cyclical growth
Authors: Bergstrom A. R. 
Published: September 2002

AbstractThis paper is concerned with the stability of macroeconomic models in which there is no long‐run trade‐off between unemployment and inflation, because of a wage adjustment equation based on the NAIRU concept. It is shown, for a simple theoretical model and for the Bergstrom–Nowman–Wymer continuous‐time macro‐econometric model of the UK, that there is a bounded range of positive values of the wage acceleration parameter (determining the effect of labour demand on wage acceleration) for which the steady state is asymptotically stable. Then, each model generates damped cycles about a path converging to the steady‐state neoclassical growth path. Copyright © 2001 John Wiley & Sons, Ltd.
Descriptive econometrics for non‐stationary time series with empirical illustrations
Authors: Phillips Peter C. B. 
Published: September 2002

AbstractRecent work by the author on methods of spatial density analysis for time series data with stochastic trends is reviewed. The methods are extended to include processes with deterministic trends, formulae for the mean spatial density are given, and the limits of sample moments of non‐stationary data are shown to take the form of moments with respect to the underlying spatial density, analogous to population moments of a stationary process. The methods are illustrated in some empirical applications and simulations. The empirical applications include macroeconomic data on inflation, financial data on exchange rates and political opinion poll data. It is shown how the methods can be used to measure empirical hazard rates for inflation and deflation. Empirical estimates based on historical US data over the last 60 years indicate that the predominant inflation risks are at low levels (2–6%) and low two‐digit levels (10–12%), and that there is also a significant risk of deflation around the −1% level. Copyright © 2001 John Wiley & Sons, Ltd.