bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro and in vivo studies of the anticancer action of terbinafine in human cancer cell lines: G0/G1 p53‐associated cell cycle arrest
Authors: Lee Wen‐Sen , Chen Rong‐Jane , Wang Ying‐Jan , Tseng How , Jeng Jiiang‐Huei , Lin Shyr‐Yi , Liang Yu‐Chih , Chen Chien‐Ho , Lin Chien‐Huang , Lin Jen‐Kun , Ho Pei‐Yin , Chu Jan‐Show , Ho Wei‐Lu , Chen Li‐Ching , Ho Yuan‐Soon 
Published: June 2003

AbstractTerbinafine (TB) (Lamisil®), a promising oral antifungal agent used worldwide, has been used in the treatment of superficial mycosis. In our study, we demonstrated that TB dose‐dependently decreased cell number in various cultured human malignant cells. Flow cytometry analysis revealed that TB interrupts the cell cycle at the G0/G1 transition. The TB‐induced cell cycle arrest in colon cancer cell line (COLO 205) occurred when the cyclin‐dependent kinase (cdk) system was inhibited just as the levels of p53, p21/Cip1 and p27/Kip1 proteins were augmented. In the TB‐treated COLO 205, the binding between p53 protein and p53 consensus binding site in p21/Cip1 promoter DNA probe was increased. Pretreatment of COLO 205 with p53‐specific antisense oligodeoxynucleotide decreased the TB‐induced elevations of p53 and p21/Cip1 proteins, which in turn led to arrest in the cell cycle at the G0/G1 phase. Moreover, in the p53 null cells, HL60, TB treatment did not induce cell cycle arrest. Taken together, these results suggest an involvement of the p53‐associated signaling pathway in the TB‐induced antiproliferation in COLO 205. We further examined whether administration of TB could affect the growth of tumors derived from human colon cancer cells in an in vivo setting. COLO 205 cells implanted subcutaneously in nude mice formed solid tumor; subsequent intraperitoneal injections of TB (50 mg/kg) led to obvious decline in tumor size, up to 50–60%. In these tumors, increases in the p21/Cip1, p27/Kip1 and p53 proteins and the occurrence of apoptosis were observed. Combined treatment with TB and nocodazole (ND), a clinically used anticancer agent, potentiated the apoptotic effect in COLO 205. These findings demonstrate for the first time that TB can inhibit the proliferation of tumor cells in vitro and in vivo. © 2003 Wiley‐Liss, Inc.
Malignant tumors in first‐degree relatives of cancer patients aged 0–25 years (province of Trieste, Italy)
Authors: Brunetti Davide , Tamaro Paolo , Cavallieri Furio , Stanta Giorgio 
Published: June 2003

AbstractTo determine whether the occurrence of first and second primary malignancies in first‐degree relatives of cancer patients aged 0–25 years (probands) differed from that in the general population, a cohort study was carried out on 860 relatives of 265 probands living in the province of Trieste, Italy. During the follow‐up period (median duration = 28 years, 25th–75th percentile = 20–34), the relatives developed 103 first primary cancers vs. 88.9 expected for a standardized incidence ratio (SIR) of 1.2 (p = 0.2). Significantly elevated risks were found for melanoma in the parents of probands aged 15–25 years with melanoma (SIR = 15.0, p = 0.002), for hemolymphatic malignancies in the fathers of probands aged 0–14 years with brain tumors (SIR = 13.3, p = 0.0005) and for hemolymphatic cancers in relatives as a whole of probands aged 15–25 years with lymphomas (SIR = 4.5, p = 0.01). During the follow‐up period, 7 relatives with a first primary cancer had a subsequent malignancy vs. 4.2 expected for an SIR of 1.7 (p = 0.3). Our results indicate that young cancer patients per se should not to be considered as a factor that usually increases the risk of developing malignant tumors among their first‐degree relatives, except when a known cancer family syndrome or predisposition is recognized. © 2003 Wiley‐Liss, Inc.
Exclusion of BRAFV599E as a melanoma susceptibility mutation
Authors: Meyer Peter , Klaes Ruediger , Schmitt Christina , Boettger Melanie Barbara , Garbe Claus 
Published: June 2003

AbstractVery recently, BRAF mutations were found in about 2/3 of malignant melanomas and at lower frequencies in other human cancers. The BRAF gene codes for a protein in the mitogen‐activated protein kinase (MAPK) pathway. All mutations identified to date are within the kinase domain, with a single missense mutation (V599E) accounting for 80%. We investigated the hypothesis that this common somatic BRAF mutation (V599E) would contribute to melanoma predisposition in familial and polygenic malignant melanoma if occuring as a germ‐line mutation. We performed comprehensive mutational screening of exon 15 of BRAF using DHPLC (denaturing high‐performance liquid chromatography) and DNA sequencing techniques. No V599E mutation could be detected in 172 melanoma patients comprising 46 familial cases, 21 multiple melanoma patients and 106 cases with at least one first‐degree relative suffering from other cancers. We therefore conclude that the common somatic BRAF mutation V599E does not contribute to polygenic and familial melanoma predisposition. © 2003 Wiley‐Liss, Inc.
Vitamin D enhances caspase‐dependent and ‐independent TNFα‐induced breast cancer cell death: The role of reactive oxygen species and mitochondria
Authors: Weitsman Gregory E. , Ravid Amiram , Liberman Uri A. , Koren Ruth 
Published: June 2003

AbstractCalcitriol, the hormonal form of vitamin D, potentiates the activity of some common anticancer drugs and agents of the anticancer immune system, including tumor necrosis factor α (TNFα). TNFα‐induced cytotoxicity is due to both caspase‐dependent and ‐independent pathways. Cotreatment with calcitriol enhanced both modes of TNFα‐induced death in MCF‐7 breast cancer cells. It increased caspase‐3‐like activity as assayed by the cleavage of poly‐(ADP‐ribose)polymerase and of the fluorogenic substrate ac‐DEVD‐AMC. It also enhanced TNFα‐induced caspase‐independent cytotoxicity in the presence of the pan‐caspase inhibitor zD‐2,6‐dichlorobenzoyloxymethylketone. The antioxidants N‐acetylcysteine, reduced glutathione, lipoic acid and ascorbic acid markedly reduced the enhancing effect of the hormone on TNFα‐induced caspase activation. N‐acetylcysteine and reduced glutathione also decreased caspase‐independent cytotoxicity in the presence or absence of calcitriol, indicating that reactive oxygen species (ROS) have a key role in the cross talk between TNFα and calcitriol. Mitochondrial damage is common to both TNFα‐induced caspase‐dependent and ‐independent pathways and may underlie excessive production of ROS. Mitochondrial membrane potential (ΔΨ) was assessed by the specific potential‐sensitive fluorescent probe JC‐1. The hormone augmented the drop in ΔΨ and release of cytochrome c from mitochondria, induced by TNFα. The effect of calcitriol on ΔΨ was mimicked by rotenone, which increased both the drop in ΔΨ and caspase activation induced by TNFα. It is possible that the interaction of TNFα and calcitriol on the level of the mitochondria is the underlying mechanism responsible for the enhancement of TNFα‐induced, ROS‐mediated caspase‐dependent and ‐independent cell death. © 2003 Wiley‐Liss, Inc.
Induction of apoptosis and chemosensitization of mesothelioma cells by Bcl‐2 and Bcl‐xL antisense treatment
Authors: Hopkins‐Donaldson Sally , Cathomas Richard , Simões‐Wüst A. Paula , Kurtz Stefanie , Belyanskya Larisa , Stahel Rolf A. , Zangemeister‐Wittke Uwe 
Published: June 2003

AbstractOur study was designed to investigate the role of the anti‐apoptotic proteins Bcl‐2 and Bcl‐xL in the chemoresistance of cells derived from malignant pleural mesothelioma. First, we determined the basal expression levels of Bcl‐2 and Bcl‐xL in mesothelioma cells and examined the effect of their downregulation by antisense oligonucleotides. Bcl‐xL mRNA and protein could be readily detected in mesothelioma cell lines, whereas only low levels of Bcl‐2 mRNA and protein were found. Preferential downregulation of either Bcl‐xL alone or of Bcl‐xL and Bcl‐2 simultaneously was achieved by treatment with antisense oligonucleotides 4259 and 4625, respectively, whereas the expression of other apoptosis‐relevant genes remained unaffected. Treatment with oligonucleotides 4259 or 4625 lowered the apoptosis threshold in ZL34 mesothelioma cells, as indicated by an increase in cell death accompanied by increased caspase‐3‐like activity, a decrease of the mitochondrial transmembrane potential and the cleavage of procaspase‐7 and ICAD. In addition to the direct induction of apoptosis, antisense treatment sensitized ZL34 cells to the cytostatic effect of cisplatin and gemcitabine, with the combination of 4625 and cisplatin being the most effective. Our results demonstrate that Bcl‐2 and Bcl‐xL antisense treatment facilitates apoptosis in mesothelioma cells and suggest the use of Bcl‐2/Bcl‐xL bispecific antisense treatment in combination with cisplatin or gemcitabine for therapy of malignant pleural mesothelioma. © 2003 Wiley‐Liss, Inc.
Childhood exposure to simian virus 40‐contaminated poliovirus vaccine and risk of AIDS‐associated non‐Hodgkin's lymphoma
Authors: Engels Eric A. , Rodman Leonard H. , Frisch Morten , Goedert James J. , Biggar Robert J. 
Published: June 2003

AbstractPersons with acquired immunodeficiency syndrome (AIDS) have increased risk for non‐Hodgkin's lymphoma (NHL). Recent studies have reported the detection of DNA sequences from simian virus 40 (SV40), a macaque polyomavirus that contaminated early poliovirus vaccines, in a large proportion of AIDS‐associated NHLs. To examine the association between SV40 exposure and NHL risk, we analyzed data from a U.S. registry‐based cohort study of persons with AIDS (1980–96). We calculated NHL incidence in persons born in 1958–61 (exposed to SV40‐contaminated poliovirus vaccine as children, n = 39,468) and in 1964–67 (born after vaccines were cleared of SV40 and thus unexposed, n = 17,340). Among persons with AIDS, NHL incidence was 11.7 per 1,000 person‐years in SV40‐exposed individuals (616 NHL cases) and 10.1 per 1,000 person‐years in SV40‐unexposed individuals (230 cases; unadjusted relative risk 1.15, 95% CI 0.99–1.34, p = 0.06). Because of differences in cohorts' birth years and the evolving demographics of the AIDS epidemic, SV40‐exposed subjects were older at AIDS onset than unexposed subjects (mean age 32.0 vs. 27.2 years, p < 0.0001), and the cohorts differed by sex (p < 0.0001) and ethnic group (p < 0.0001). Since NHL incidence was relatively high among whites (p < 0.0001) and homosexual males (p < 0.0001) and increased with age (p = 0.09), comparisons required adjustments for these factors. After adjustment, SV40 exposure was not associated with NHL incidence (adjusted relative risk 0.97, 95% CI 0.79–1.20, p = 0.80). We conclude that childhood exposure to SV40 through receipt of contaminated poliovirus vaccine was not associated with increased risk for AIDS‐associated NHL. Our findings do not support a role for SV40 in lymphomagenesis among immunosuppressed persons. © 2003 Wiley‐Liss, Inc.
Familial brain tumours—genetics or environment? A nationwide cohort study of cancer risk in spouses and first‐degree relatives of brain tumour patients
Authors: Malmer Beatrice , Henriksson Roger , Grönberg Henrik 
Published: June 2003

AbstractOur study investigated whether the familial aggregation of glioma is due to environmental or genetic effects and it investigated and compared the risk to spouses and first‐degree relatives (FDR) of patients with primary brain tumours (PBT) for developing both PBT and the risk for other types of cancer. All PBT patients identified in Sweden from 1958–97 in The Swedish Cancer Registry (SCR) were linked to the nationwide Swedish Family Database, including persons in Sweden born from 1932–97. The cohorts of spouses and FDR were linked to the SCR to identify observed cases of PBT and other cancer. Standardised incidence ratios (SIR) were calculated using the incidence rates from SCR as the reference. We found that there were no increased risks for any specific type of PBT in the cohort of spouses. In the FDR cohort, generally the risk for a PBT was significantly increased by 2 to 3 times for the same histopathology as the probands. Spouses of PBT patients had an increased risk of skin cancer. We conclude that FDR, not spouses, have a significantly increased risk, which indicates a genetic origin of the familial aggregation of brain tumours. © 2003 Wiley‐Liss, Inc.
Ectopic chromosome around centrosome in metaphase cells as a marker of high‐risk human papillomavirus–associated cervical intraepithelial neoplasias
Authors: Furuta Reiko , Hirai Yasuo , Katase Katsuyoshi , Tate Shinichi , Kawaguchi Tokuichi , Akiyama Futoshi , Kato Yo , Kumada Kazuki , Iwasaka Tsuyoshi , Yaegashi Nobuo , Kanazawa Koji , Yoshikawa Hiroyuki , Kitagawa Tomoyuki 
Published: June 2003

AbstractThis report describes the appearance of ectopic chromosome around centrosome (ECAC) in metaphase cell nuclei of high‐risk HPV‐associated cervical neoplasms. ECAC are clearly visible on HE‐stained sections as a tiny (approx. 0.7 μ), round, dark structure or an aggregate of filamentous chromosome, often symmetrical at bilateral centrosomes. They appear in CINs from an early stage (CIN I), with the highest incidence in HPV16‐associated CIN II–III (75%), and are less common in HPV‐related invasive carcinomas (21%) and in lesions associated with high‐risk HPV types other than 16. Rates for ECAC‐positive nuclei in metaphase preparations (ECAC rate) for each lesion ranged 3.6–30%, the average being 14.5%. ECAC appeared very rarely in CINs associated with intermediate‐risk HPVs and was never encountered in HPV6/11‐induced condylomas or HPV‐unrelated neoplasms in other organs. ECAC may be morphologic evidence of HPV‐induced chromosomal instability working as a background mechanism in cervical carcinogenesis and also a useful marker for the histopathologic differentiation of high‐risk CINs. © 2003 Wiley‐Liss, Inc.
Selective expression of HLA‐G in malignant and premalignant skin specimens in kidney transplant recipients
Authors: Aractingi Sélim , Kanitakis Jean , Euvrard Sylvie , Le Danff Caroline , Carosella Edgardo D. 
Published: June 2003

AbstractThe HLA‐G molecule has been implicated in the escape from the host antitumor immune response. Besides, this molecule appears also to be detected in transplant recipient's tissues, mainly those with fewer rejection episodes. Since skin carcinomas develop frequently in organ transplant recipients, we asked whether HLA‐G could be expressed in these lesions, therefore allowing tumor development in such patients. Immunohistochemical analysis of kidney transplant recipients presenting various types of epithelial malignant tumor and benign cutaneous lesion was done using a specific anti‐HLA‐G antibody. HLA‐G was expressed in 35% of specimens of SCC, 47% of in situ carcinoma, 27% of AK and 14% of BCC but never in the 24 benign lesions studied. Many benign specimens were obtained from the same patients who had tumors, demonstrating that HLA‐G expression was restricted to the malignant sites. Interestingly, HLA‐G was expressed by proliferative keratinocytes, inflammatory infiltrates and even endothelial cells. Cytokines triggered in the course of organ transplantation include IL‐10. This molecule may induce expression of HLA‐G, which in turn may be implicated in tumor development in transplanted recipients. © 2003 Wiley‐Liss, Inc.
Little evidence for involvement of MLH3 in colorectal cancer predisposition
Authors: Hienonen Tuija , Laiho Päivi , Salovaara Reijo , Mecklin Jukka‐Pekka , Järvinen Heikki , Sistonen Pertti , Peltomäki Päivi , Lehtonen Rainer , Nupponen Nina N. , Launonen Virpi , Karhu Auli , Aaltonen Lauri A. 
Published: June 2003

AbstractMutations in the DNA MMR genes MSH2, MLH1, MSH6 and PMS2 underlie a large subset of HNPCC cases, and a hallmark of the tumors is MSI. In many HNPCC families, however, a causative mutation has not been found. Therefore, the involvement of additional, thus far unknown, genes in MSI as well as MSS colorectal tumor predisposition is possible. The role of a relatively recently cloned MMR gene, MLH3, in familial CRC has been studied; but the results appear somewhat conflicting. To further evaluate the role of MLH3 in CRC predisposition, we analyzed 30 Finnish CRC cases for germline mutations by sequencing. These cases were selected from a large series of Finnish CRC patients, to match features previously proposed to associate with MLH3 germline defects. We found 5 missense variants, 4 of which were also found in Finnish cancer‐free controls. The only remaining variant does not appear to be an attractive candidate for a disease‐associated mutation because the amino acid change is located outside the conserved residues. We also screened for the previously reported variants, including a frameshift change, the most likely pathogenic MLH3 mutation observed so far. The frameshift was not present in the 30 CRC cases or in 700 cancer‐free controls. While it is a difficult task to exclude a role of MLH3 in HNPCC, our study could not confirm a role for MLH3 in CRC predisposition. © 2003 Wiley‐Liss, Inc.
Increasing use of seat belts among kindergarten children: Skills beyond awareness
Authors: Gidron Yori , Hochberg Ronny 
Published: June 2003

AbstractParticipatory learning was previously found to increase seat belt use by children. However, cross‐cultural generalizability, effects of intervention beyond enhancing awareness, and risk factors for nonuse of seat belts, were not addressed. This study examined the effects of such an intervention on seat belt use, and addressed these issues in an Israeli kindergarten. One week, and 1 day before the intervention, 29 and 20%, respectively, of children were fastened by parents. Significant increases were seen 1 day (71%) and 1 month after the intervention (65%). The intervention's effects generalize to an Israeli sample, are not merely due to enhancing awareness, and maintain over time. © 2003 Wiley Periodicals, Inc. J Comm Psychol 31: 315–319, 2003.
Client choice of treatment and client outcomes
Authors: Calsyn Robert J. , Morse Gary A. , Yonker Robert D. , Winter Joel P. , Pierce Kathy J. , Taylor Matthew J. 
Published: June 2003

AbstractParticipants in this study suffered from severe mental illness and were homeless at baseline. They were given their choice of five different treatment programs. The current study investigated two major questions: (1) what is the impact of positive expectancies about the efficacy of the chosen program on number of contacts with the chosen program and client outcomes; and (2) what is the impact of positive views about nonchosen programs (alternative choice variables) on contact with the chosen program and client outcomes. Client outcomes assessed were psychotic symptoms, days homeless, and client satisfaction. Positive expectancy variables were the number of reasons for choosing a program and confidence that the program would help. Alternative choice variables were the number of nonchosen programs visited and the attractiveness of a nonchosen program. Only the number of reasons for choosing the program was significantly related to program contact with the chosen program. Both of the positive expectancy variables and program contact were significantly correlated with consumer satisfaction. In general, neither the positive expectancy variables nor the alternative choice variables predicted changes in psychotic symptoms nor days homeless. © 2003 Wiley Periodicals, Inc. J Comm Psychol 31: 339–348, 2003.
Changing contexts? The effects of a primary prevention program on classroom levels of peer relational and physical victimization
Authors: Leadbeater Bonnie , Hoglund Wendy , Woods Tom 
Published: June 2003

AbstractWhereas school‐based prevention programs often target deficits in individual children's social skills in order to limit their aggression or exposure to peer victimization, there is increasing evidence that school‐wide and classroom‐level factors can also affect the success of these programs. This short‐term longitudinal study involved 432 elementary school students from 44 classrooms in 17 urban schools. We investigated whether classroom characteristics (average levels of social competence, emotional problems, and behavioral problems) and school‐wide characteristics (proportion of children on income assistance and implementation of a peer victimization prevention program—the Walk away, Ignore, Talk, and Seek help [W.I.T.S.] program) experienced in Grade 1 influences changes in children's reports of relational and physical victimization at the end of Grade 2. Findings showed that classroom levels of emotional problems predicted increases in relational victimization (beyond individual differences in emotional and behavioral problems). Classroom levels of behavioral problems predicted reports of increases in physical victimization (beyond individual differences). Classroom levels of social competence also interacted with individual levels of emotional problems such that children with higher levels of emotional problems in classes with more socially competent children reported more relational and physical victimization. Higher school levels of poverty and lack of program involvement also predicted higher levels of physical victimization, beyond individual and classroom effects. The capacity of the W.I.T.S. program to influence classroom level characteristics and the moderating effects of school poverty on victimization were also assessed. © 2003 Wiley Periodicals, Inc. J Comm Psychol 31: 397–418, 2003.
Depletion of mitochondrial DNA in HIV‐1‐infected patients and its amelioration by antiretroviral therapy
Authors: Miura Toshiyuki , Goto Mieko , Hosoya Noriaki , Odawara Takashi , Kitamura Yoshihiro , Nakamura Tetsuya , Iwamoto Aikichi 
Published: June 2003

AbstractMitochondrial DNA (mtDNA) of peripheral blood mononuclear cells (PBMCs) collected from Human immunodeficiency virus 1 (HIV‐1)‐infected patients and healthy controls were measured longitudinally using real‐time polymerase chain reaction to evaluate the effects of antiretroviral agents on mtDNA synthesis in vivo and to assess the value of monitoring mtDNA in PBMCs to predict adverse events amongst these patients. MtDNA levels in PBMCs were significantly decreased in treatment‐naive HIV‐1‐infected patients compared with healthy people. MtDNA levels were not only significantly correlated with CD4+ T‐cell count, but also inversely correlated with HIV‐1 viral load. MtDNA levels in untreated patients and healthy controls were stable during the period of observation. On the other hand, amongst patients treated with regimens containing AZT/3TC or d4T/3TC, mtDNA increased during treatment and recovered to levels comparable to healthy controls. In contrast, mtDNA decreased immediately after the initiation of an AZT/ddC‐containing regimen. We did not find a correlation between mtDNA levels and changes in clinical parameters. There was no significant difference in mtDNA levels between patients with and those without lipoatrophy. Furthermore, there was no obvious difference in mtDNA levels amongst those patients exhibiting signs and symptoms of peripheral neuropathy. In conclusion, the decrease in mtDNA levels in PBMCs amongst HIV‐1‐infected patients and its amelioration by antiretroviral therapy may suggest the influence of direct effects on mitochondria or mtDNA by HIV‐1 infection. Further investigations are needed to elucidate the mechanisms contributing to decreased mtDNA and the value of mtDNA measurement in the care of HIV‐1‐infected individuals. J. Med. Virol. 70:497–505, 2003. © 2003 Wiley‐Liss, Inc.