bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural killer cell cytolytic activity is necessary for in vivo antitumor activity of the dipeptide L‐glutamyl‐L‐tryptophan
Authors: Smith D. Lynne , Cai Jie , Zhu SuTao , Wei Wen , Fukumoto Jon , Sharma Sanjai , Masood Rizwan , Gill Parkash S. 
Published: July 2003

AbstractA dipeptide, L‐glutamyl L‐tryptophan (L‐glu‐L‐trp), was identified in a screen for immunomodulators in the soluble fraction of the thymus. L‐glu‐L‐trp inhibits tumor growth in mice without showing direct cellular toxicity in a variety of human tumor cell lines. L‐glu‐L‐trp antitumor activity in vivo requires the presence of natural killer (NK) cells. Defective trafficking of cytoplasmic granules caused by the Lyst mutation also resulted in loss of antitumor activity of the dipeptide. The effect of L‐glu‐L‐trp on tumor growth in mice with targeted gene mutations demonstrated the absolute requirement for perforin for antitumor activity. The requirement of 2 major modulators of NK cell activity, gamma interferon (IFNγ) and interleukin (IL)‐12, were also tested. L‐glu‐L‐trp had full antitumor activity in IFNγ knockout mice, but had significantly diminished activity in IL‐12 knockout mice. These data show that L‐glu‐L‐trp antitumor activity in mice is dependent on cytolytic cell activity of NK or NKT cells. L‐glu‐L‐trp in vivo regulates NK cell function independent of IFNγ but partly dependent on IL‐12. © 2003 Wiley‐Liss, Inc.
Invasion of melanoma cells into dermal connective tissue in vitro: Evidence for an important role of cysteine proteases
Authors: Dennhöfer Ralf , Kurschat Peter , Zigrino Paola , Klose Anke , Bosserhoff Anja , van Muijen Goos , Krieg Thomas , Mauch Cornelia , Hunzelmann Nicolas 
Published: July 2003

AbstractInvasion of melanoma cells into the dermal connective tissue is a major characteristic in the complex process of metastasis. Proteases play an important role in tumor cell invasion as these enzymes are able to degrade most components of the extracellular matrix (ECM), and thus enable cells to penetrate interstitial connective tissues and basement membranes. We developed an improved culture model that allows the detailed study of melanoma cell invasion in vitro. In this model, high (BLM) or low (530) invasive melanoma cells were seeded on the dermal side of dead deepidermized dermis (DDD) and cultured for 14 days at the air/liquid interface. The high invasive cells invaded the tissue, leading to dermal tumor formation, whereas the low invasive cells did not. Analysis of the enzymatic activity of gelatinases by in situ gelatin zymography at neutral pH revealed proteolysis only in those composites cultured with high invasive melanoma cells. Interestingly, in situ zymograms performed at more acidic conditions, favoring the activity of cysteine proteases, exhibited markedly enhanced and widespread gelatinolysis compared to neutral pH. Cysteine protease inhibitors (E‐64 and leupeptin) significantly reduced invasion of melanoma cells into these composites. These results indicate an important role of cysteine proteases for tumor invasion. © 2003 Wiley‐Liss, Inc.
Antitumor and antimetastatic activities of Angelica keiskei roots, part 1: Isolation of an active substance, xanthoangelol
Authors: Kimura Yoshiyuki , Baba Kimiye 
Published: July 2003

AbstractThe roots of Angelica keiskei Koizumi have traditionally been used as a health food, with diuretic, laxative, analeptic and galactagogic effects. It has been thought that the roots and leaves of A. keiskei have preventive effects against coronary heart disease, hypertension and cancer. In the present study, we examined the antitumor and antimetastatic activities of various fractions isolated from a 50% ethanol extract of A. keiskei roots. The ethyl acetate‐soluble fraction of the 50% ethanol extract inhibited tumor growth in LLC‐bearing mice at a daily dose of 100 mg/kg prolonged survival time and inhibited metastasis to the lung after surgical removal of primary tumors. Two active substances were isolated from fractions 1 and 2: compound 1 was identified as xanthoangelol based on the data of the 1H‐ and 13C‐NMR spectra. Xanthoangelol inhibited tumor growth in LLC‐bearing mice as well as lung metastasis and prolonged survival time in carcinectomized mice at a daily dose of 50 mg per kg. Furthermore, xanthoangelol (50 or 100 mg per kg daily) inhibited liver metastasis and the growth of metastasized tumor cells in the livers of mice with intrasplenically implanted LLC. Xanthoangelol inhibited DNA synthesis in LLC cells at concentrations of 10 and 100 μM, but it had no effect on DNA synthesis in HUVECs or on the adherence of LLC cells to HUVECs. Xanthoangelol inhibited tumor‐induced neovascularization (in vivo) at doses of 10 and 20 mg per kg, and it inhibited the Matrigel‐induced formation of capillary‐like tubes by HUVECs at concentrations of 1–100 μM. Furthermore, xanthoangelol inhibited the binding of VEGF to HUVECs at concentrations of 1–100 μM. These results indicate that the antitumor and/or antimetastatic activities of xanthoangelol may be due to inhibition of DNA synthesis in LLC cells and of tumor‐induced neovascularization through inhibition of the formation of capillary‐like tubes by vascular endothelial cells and inhibition of the binding of VEGF to vascular endothelial cells. © 2003 Wiley‐Liss, Inc.
Bidi smoking and oral cancer: A meta‐analysis
Authors: Rahman Mahbubur , Sakamoto Junichi , Fukui Tsuguya 
Published: July 2003

AbstractSeveral epidemiological studies suggest that bidi smoking increases the risk of oral cancer. No systematic review, however, has been reported to examine how consistent the evidence is across the studies. We undertook a meta‐analysis of epidemiological studies investigating the relationship between bidi smoking and oral cancer. Primary studies were identified through a computerized literature search of Medline. Articles abstracted were all epidemiological studies published as original articles in English during 1966–2002 that included quantitative information on bidi smoking and oral cancer. Summary odds ratios (OR) were calculated based on random effects model. A total of 12 case‐control studies used for this meta‐analysis provided the summary estimates of OR of bidi smoking for oral cancer compared to that of non‐smokers. An increased risk of oral cancer was found for bidi smokers compared to never smokers (OR = 3.1, 95% confidence interval [CI] 2.0–5.0) whereas no significant pattern of risk was found for cigarette smokers (OR = 1.1, 95% CI = 0.7–1.8). There was substantial heterogeneity in the pooled OR estimate. Our results clearly indicate that bidi smokers are at increased risk of oral cancer. It is important that this information be incorporated into smoking prevention and cessation efforts, particularly among the urban poor and rural mass in South Asian countries where bidi smoking is widely prevalent. © 2003 Wiley‐Liss, Inc.
Identification of tumor‐associated antigens by screening phage‐displayed human cDNA libraries with sera from tumor patients
Authors: Minenkova Olga , Pucci Andrea , Pavoni Emiliano , De Tomassi Amedeo , Fortugno Paola , Gargano Nicola , Cianfriglia Maurizio , Barca Stefano , De Placido Sabino , Martignetti Angelo , Felici Franco , Cortese Riccardo , Monaci Paolo 
Published: July 2003

AbstractScreening cDNA libraries from solid human tumors with sera of autologous patients (SEREX) has proven to be a powerful approach to identifying tumor antigens recognized by the humoral arm of the immune system. In many cases, application of this methodology has led to the discovery of novel tumor antigens as unknown gene products. We tried to improve the potency of the SEREX approach by combining it with phage‐display technology. We designed a new lambda vector to express protein fragments as N‐terminal fusions to the D capsid protein and generated high‐complexity cDNA libraries from human breast carcinoma cell lines and solid tumors. Screening these phage‐displayed libraries required limited amounts of sera from patients and efficiently identified several tumor antigens specifically reacting with sera from breast cancer patients. © 2003 Wiley‐Liss, Inc.
Rapid onset of nucleolar disintegration preceding cell cycle arrest in roscovitine‐induced apoptosis of human MCF‐7 breast cancer cells
Authors: Wojciechowski Jacek , Horky Marcel , Gueorguieva Marieta , Węsierska‐Gądek Józefa 
Published: July 2003

AbstractThe aim of our study was to explore the antiproliferative and pro‐apoptotic action of roscovitine (ROSC) on human breast cancer MCF‐7 cells. We examined the effect of ROSC on cell proliferation, cell cycle progression, nucleolar morphology, posttranslational modifications of histones as well as on induction of apoptosis. The effects of ROSC on the argyrophilic nucleolar organizer regions (AgNORs) and nucleolar RNA of MCF‐7 cells were marked: ROSC treatment changed the pattern of AgNORs in a time‐dependent manner. The disintegration of nucleoli manifested by increasing number of nucleolar fragments already began at 6 hr posttreatment. This was accompanied by a redistribution of the nucleolin from the nucleolus beginning after 6 hr and preceded a decrease of histone acetylation and phosphorylation. Inhibition of DNA synthesis and accumulation of G2/M‐arrested cells starting 6 hr posttreatment coincided with a strong increase of the p53 level and with an appearance of a few cells committed to undergo apoptosis. However, all these changes preceded the main wave of apoptosis, which occurred after 24 hr ROSC treatment as assessed by determination of the frequency of Annexin binding, activation of caspases as well as of DNA fragmentation. Onset of PARP‐1 cleavage detected by immunoblotting and by immunohistochemistry 6 hr or 9 hr posttreatment, respectively, preceded for a few hours the DNA fragmentation detected in situ by TUNEL assay. Reconstitution of MCF‐7 cells with caspase‐3 did not change the kinetics of ROSC‐induced apoptosis. Our results show that disintegration of nucleoli is an early marker of ROSC‐induced changes. Cell cycle arrest precedes the main wave of apoptosis. © 2003 Wiley‐Liss, Inc.
Immunocytochemical analysis of the circadian clock protein in mouse hepatocytes
Authors: Malatesta Manuela , Baldelli Beatrice , Marcheggiani Francesco , Gazzanelli Giancarlo 
Published: July 2003

AbstractMany biochemical, physiological, and behavioral processes in organisms ranging from prokaryotes to humans exhibit circadian rhythms, defined as cyclic oscillations of about 24 hours. The mechanism of the cellular circadian clock relies on interlocking positive and negative transcriptional/translational feedback loops based on the regulated expression of several genes. Clock is one of these genes and its transcript, CLOCK protein, is a transcription factor belonging to the bHLH‐PAS family. In mammals the clock gene is expressed in several tissues, including the liver. In the present study, we analyzed by means of quali‐quantitative immunoelectron microscopy the fine intracellular distribution of the CLOCK protein in mouse hepatocytes during the daily cycle. We demonstrated that CLOCK protein is mostly located in the cell nucleus, where it accumulates on perichromatin fibrils, representing the in situ form of nascent pre‐mRNA, while condensed chromatin and nucleoli contain lower amounts of protein. Moreover, we found that CLOCK protein shows circadian oscillations in these nuclear compartments, peaking in late afternoon. At this time the hepatic transcriptional rate reaches the maximal level, thus suggesting an important role of CLOCK protein in the regulation of liver gene expression. Microsc. Res. Tech. 61:414–418, 2003. © 2003 Wiley‐Liss, Inc.
Managing for competitiveness: a proposed model for managerial focus
Authors: Connor Tom 
Published: July 2003

Abstract

The word competitiveness is used extensively in management discourse concerning national economic performance, international economic performance comparisons and at the level of the firm.
It is a word of elusive meaning. Indeed, it is used in so many different ways that there must be serious doubt that the word has any concrete meaning at all. This is regrettable because it could make a valuable contribution to our thinking about economic policy and the management of business.
This paper considers the concept of competitiveness at the level of the business unit and proposes an interpretation, which will be of value to practising managers in their efforts to improve the economic performance of their businesses.

Copyright © 2003 John Wiley & Sons, Ltd.
Why bother to be better? strategically stagnant personal current accounts
Authors: Martin Stephen , Mainelli Michael 
Published: July 2003

Abstract

Banks are keen to supply current accounts because apart from direct income, they are more successful in selling a wide range of their financial services to customers who possess a current account.
The UK market for current accounts appears to exhibit little customer movement and is dominated by 4 out of at least 140 suppliers, despite variable levels of service.
Using Prospect Theory, attempts are made to explain why this market is so stagnant and to suggest how suppliers could be more successful at promoting change.
Results suggest that changing the initial perceptions of customers will have more impact than trying to induce customers to change suppliers by promoting the benefits of an alternative bank.

Copyright © 2003 John Wiley & Sons, Ltd.
c‐erbB‐4/HER4: friend or foe?
Authors: Gullick William J 
Published: July 2003

AbstractThe c‐erbB‐4 receptor has ligand stimulated tyrosine kinase activity but reports differ as to whether it induces cell division or differentiation. There is also controversy regarding its role in breast cancer, with some reports associating overexpression with short survival and others with longer life. Copyright © 2003 John Wiley & Sons, Ltd.
Impaired hepatic granuloma formation in mice deficient in C–C chemokine receptor 2
Authors: Jinnouchi Katsunori , Terasaki Yasuhiro , Fujiyama Shigetoshi , Tomita Kimio , Kuziel William A , Maeda Nobuyo , Takahashi Kiyoshi , Takeya Motohiro 
Published: July 2003

AbstractGranulomas are characterized histologically by a nodular collection of macrophages with occasional admixture of epithelioid cells, multinucleate giant cells, and other immunocompetent cells. Chemokines are considered to play an important role in the recruitment of these constituent cells of granulomas. The present study has examined the effect of a deficiency of C–C chemokine receptor‐2 (CCR2) on hepatic granuloma formation induced by a single injection of Zymosan A. In CCR2+/+ mice, the number and the size of granulomas gradually increased until they reached peak values at 10 days after the injection. In contrast, both the number and the size of granulomas were smaller in CCR2−/− mice than in CCR2+/+ mice from days 5 to 21. They showed low peaks at day 5, after which the number and the size of the granulomas gradually decreased. Immunohistochemical analysis of the constituent granuloma cells using cell type‐specific monoclonal antibodies revealed rapid accumulation of blood monocytes, with subsequent differentiation to macrophages, in CCR2+/+ mice during days 2–10. This process was greatly impaired in CCR2−/− mice and granulomas remained small. At all time points, the percentage of polymorphonuclear cells in granulomas was higher in CCR2−/− mice than in CCR2+/+ mice. Interestingly, multinucleate giant cells were frequently observed in granulomas in CCR2−/− mice, whereas they rarely appeared in CCR2+/+ mice. Profiles of liver cytokine RNA levels as well as serum cytokine levels revealed reduced expression of the Th1 cytokine IFN‐γ in CCR2−/− mice. These data clearly indicate that signalling through CCR2 has many effects on the normal growth and development of hepatic granulomas. Copyright © 2003 John Wiley & Sons, Ltd.
In vivo and in vitro models demonstrate a role for caveolin‐1 in the pathogenesis of ischaemic acute renal failure
Authors: Mahmoudi Mitra , Willgoss Desley , Cuttle Leila , Yang Tao , Pat Betty , Winterford Clay , Endre Zoltan , Johnson David W , Gobé Glenda C 
Published: July 2003

AbstractCaveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin‐1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia–reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia–hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin‐1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin‐1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia–reperfusion. Western immunoblots indicated a marked increase in caveolin‐1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment‐induced change in both cell types was translocation of caveolin‐1 from the original plasma membrane site into membrane‐associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane‐bound, as indicated by cell fractionation analyses. Caveolin‐1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin‐1 in ARF‐induced renal injury. Whether it functions for cell repair or death remains to be elucidated. Copyright © 2003 John Wiley & Sons, Ltd.
Retracted: Autonomous histopathological regression of primary tumours associated with specific immune responses to cancer antigens
Authors: Saleh Farid H , Crotty Kerry A , Hersey Peter , Menzies Scott W , Rahman Wassim 
Published: July 2003

AbstractThis article has been retracted. See retraction notice [DOI: 10.1002/path.2082]Spontaneous histopathological regression of cancer has been reported. The involvement of the immune system in such regression has been advocated, leading to the theory of immunological surveillance against cancer. A prediction of this theory is that common tumour antigens can be recognized upon repeated exposure by cell‐mediated immunity, which leads to tumour regression and the subsequent appearance of tumour antigen‐loss variants. However, no direct evidence has been provided in non‐viral‐induced experimental animal models of primary malignancy or in human primary cancer. This study examined two groups of melanoma patients where histopathological regression of the primary tumour was observed. Many of the 23 patients with multiple (≥3) primary melanomas showed significant regression of their last melanoma (median 33%, mean 40) compared with matched melanomas from patients with a single primary melanoma (median 0%, mean 12) (p = 0.0080), or compared with their first primary melanoma (p = 0.0013). Regression was consistent with an ‘immunization effect’ seen in murine tumour transplantation studies, where inoculation with ≥3 asynchronous tumours induces transplantation rejection on subsequent challenge. A significant decrease in the expression of the melanoma common tumour antigen MART‐1 in the last primary tumour from multiple melanoma patients (median 8%, mean 24) versus matched single melanoma patients (median 79%, mean 68) (p = 0.0041) and in the last versus first tumour in multiple primary patients was found (p = 0.0083). Metastases from 17 patients whose primary skin melanomas had completely regressed (occult primary melanoma) also showed significant MART‐1 loss (median 0%, mean 11) compared with matched metastases from patients with non‐regressing primary melanoma (median 51%, mean 50) (p = 0.0013). MART‐1 antigen‐loss variants observed in the multiple primary and occult primary patients correlated with the presence of peripheral blood MART‐1‐specific cytotoxic T lymphocytes (CTLs) (p = 0.03). No similar effects were observed with two other melanoma antigens, gp100 and CD63. Thus, in two groups of human melanoma patients, evidence is provided for histopathological tumour regression associated with cancer immune surveillance. Copyright © 2003 John Wiley & Sons, Ltd.
Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer
Authors: Hoei‐Hansen Christina E , Holm Mette , Rajpert‐De Meyts Ewa , Skakkebaek Niels E 
Published: July 2003

AbstractThis study was prompted by a hypothesis that testicular germ cell cancer may be aetiologically linked to other male reproductive abnormalities as a part of the so‐called ‘testicular dysgenesis syndrome’ (TDS). To corroborate the hypothesis of a common association of germ cell cancer with testicular dysgenesis, microscopic dysgenetic features were quantified in contralateral testicular biopsies in patients with a testicular germ cell tumour. Two hundred and eighty consecutive contralateral testicular biopsies from Danish patients with testicular cancer diagnosed in 1998–2001 were evaluated retrospectively. Two hundred and eighteen specimens were subsequently included in this study, after 63 patients who did not meet inclusion criteria had to be excluded. The presence of carcinoma in situ (which is believed to originate from transformed gonocytes) was detected in 8.7% of biopsies. The incidence of other dysgenetic features was immature tubules with undifferentiated Sertoli cells, 4.6%; microcalcifications (microliths), 6.0%; and the presence of a Sertoli‐cell‐only pattern in at least a few tubules, 13.8%. The cumulative incidence of one or more signs of testicular dysgenesis was 25.2%. In a few patients, areas with immature and morphologically distorted tubules were also noted. Spermatogenesis was qualitatively normal in 51.4%, whereas 11.5% had very poor or absent spermatogenesis. It is concluded that microscopic testicular dysgenesis is a frequent feature in contralateral biopsies from patients presenting with testicular germ cell neoplasms of the adolescent and young type. The findings therefore support the hypothesis that this cancer is part of a testicular dysgenesis syndrome. The presence of contralateral carcinoma in situ was higher in the present study than previously reported. Copyright © 2003 John Wiley & Sons, Ltd.