bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous long‐term monitoring of UV radiation in professional mountain guides reveals extremely high exposure
Authors: Moehrle Matthias , Dennenmoser Bernhard , Garbe Claus 
Published: January 2003

AbstractUltraviolet radiation (UVR) is estimated to be one of the most important risk factors for nonmelanoma and melanoma skin cancers. High occupational UV exposure is assumed to be associated with skin cancer. Mountain guides receive considerable UV doses due to altitude‐related increase of UVR and reflection from snow‐ and ice‐covered surfaces. The aim of our study was to assess the annual occupational UV exposure of mountain guides. Spore film test chambers containing spores of Bacillus subtilis (VioSpor) were used as UV dosimeters with a spectral sensitivity profile similar to erythema‐weighted data calculated from spectroradiometric measurements. Nine mountain guide instructors carried dosimeters on the sides of their heads on a total of 1,406 working days during one year (July 1999–June 2000). Dosimeters were changed monthly. Measurements of 92 months could be evaluated (4–12 months/mountain guide). The mean individual monthly UV exposure was 107 standard erythema doses (SED) (median 71 SED; range 10–505 SED). The mean annual cumulative UV exposure was 1,097 SED (median 1,273 SED; range 312–1,770 SED) per mountain guide. The mean UV dose per day (4–10 hr) was 6.6 SED (median 5.7 SED; range 0.6–24.2 SED). This is the second study of continuous annual UV dosimetry in a cohort of outdoor workers. Our study showed that it is not sufficient to interpolate annual UV exposure from a few days' measurements. Only long‐term dosimetry can give reliable yearly information of UVR load. Median daily UV exposure exceeded limits for UV radiation (e.g., ACGIH effective dose 30 J/m2 per 8 hr period corresponding to 1.08 SED/day) 6‐fold; maximal exposure exceeded these limits 23‐fold. These extremely high exposure values are suggestive for an increased risk of skin cancer and thorough epidemiologic studies in the collectives of professional and recreational mountaineering are required. © 2002 Wiley‐Liss, Inc.
Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus
Authors: Wu Anna H. , Crabtree Jean E. , Bernstein Leslie , Hawtin Peter , Cockburn Myles , Tseng Chiu‐chen , Forman David 
Published: January 2003

AbstractInfection with Helicobacter pylori (H. pylori), especially CagA+ strains, has been associated with an increased risk of noncardia gastric adenocarcinoma. The relationship with junctional cancer (adenocarcinomas of the esophagus and gastric cardia combined) has not been adequately investigated, although some studies have reported a reduced risk associated with H. pylori and CagA seroseropositivity. We investigated this question in a subset of cases and controls from a recently completed, large population‐based case‐control study of gastric and esophageal adenocarcinomas in Los Angeles County. Using established antigen‐specific ELISAs, serum IgG antibodies to H. pylori whole‐cell antigens (Helico‐G) and CagA were measured in population controls (n = 356) and patients with incident esophageal adenocarcinoma (n = 80), gastric cardia cancer (n = 87) or distal gastric cancers (noncardia gastric adenocarcinoma) (n = 127). After controlling for demographic characteristics (age, gender, race, birthplace, education), smoking and body mass index, seropositivity for H. pylori was associated with a statistically significant increased risk of distal gastric cancer (adjusted odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.03, 3.32) but the risk of junctional cancer was not increased (adjusted OR = 1.26, 95% CI = 0.82, 1.94). The risk of junctional cancer was not changed when CagA and H. pylori were both considered, but the risk of distal gastric cancer was further increased. Subjects who were seropositive for both CagA and H. pylori compared to those who were seronegative for H. pylori showed a risk of 2.20 (95% CI = 1.13, 4.26) for distal gastric cancer and 0.86 (95% CI = 0.47, 1.59) for junctional cancer. Although tests for interaction between smoking and H. pylori were not statistically significant for junctional or distal gastric cancers, risk for both tumor types tended to be higher among current smokers who were also H. pylori seropositive. In conclusion, we find no evidence that infection with CagA+ strains of H. pylori reduces risk of esophageal and gastric cardia adenocarcinoma in this population. Our findings confirm the positive association between risk of distal gastric cancer and infection with H. pylori infection, especially CagA+ strains. © 2002 Wiley‐Liss, Inc.
A randomised, double‐blind, placebo‐controlled trial of photodynamic therapy using 5‐aminolaevulinic acid for the treatment of cervical intraepithelial neoplasia
Authors: Barnett Adrian A. , Haller J. Christoph , Cairnduff Fiona , Lane Geoffrey , Brown Stanley B. , Roberts David J.H. 
Published: January 2003

AbstractPhotodynamic therapy (PDT) using topical 5‐aminolaevulinic acid (ALA) has been used to treat histologically confirmed cervical intraepithelial neoplasia (CIN‐I and ‐I/II) in a randomised, double‐blind, placebo‐controlled protocol. Fluorescence microscopy revealed that topical application of 3% ALA in Intrasite Gel® to the cervix for 3 hr resulted in the accumulation of protoporphyrin IX in the cervical epithelium. Treatment of CIN with ALA‐PDT was well tolerated, with only 3/12 patients in the PDT arm (0/13 in the placebo arm) reporting any discomfort during illumination. Histologic examination of the treated tissue following loop excision 3 months post‐PDT indicated that 33% of patients had no evidence of CIN, 42% had no change in the grade of their disease, whilst 25% exhibited an apparent progression of disease. In the control group, the respective figures were 31%, 38% and 31%. There was no significant difference in response between the groups receiving ALA‐PDT and those receiving placebo treatment. © 2002 Wiley‐Liss, Inc.
Allelic imbalance at 11p15.5–15.4 correlated with c‐Ha‐ras mutation during radiation‐induced neoplastic transformation of human breast epithelial cells
Authors: Roy Debasish , Calaf Gloria , Hei Tom K. 
Published: January 2003

AbstractBreast cancer is the most frequent malignancy in women throughout much of the developed world and is associated with a multistage process involving a number of genetic mutations and their corresponding cellular phenotypic alterations. It has already been shown that neoplastic transformation of a spontaneously immortalized human breast epithelial (MCF‐10F) cell line by radiation, in combination with estrogen, represents a successful model in studying the molecular and biological alterations that may contribute to the tumorigenic process. In the present study, the incidence of allelic alterations (microsatellite instability/loss of heterozygosity) on chromosome 11 in different radiation‐induced primary and secondary tumorigenic cell lines, relative to the control MCF‐10F cells was investigated. We identified 3 regions of the chromosome 11 (11p15–p15.5, 11q13 and 11q23) that showed high incidence of LOH among these tumor cell lines and suggested a potential role for these chromosomal regions in breast carcinogenesis. Among them, locus 11p15.5, where c‐Ha‐ras oncogene is located, had incidence of allelic imbalance between 25–40%. Furthermore, direct sequencing analysis of codons 12 and 61 of the c‐Ha‐ras oncogene identified various point mutations. These data highlight the importance of chromosome 11 in radiation induced malignant transformation of human breast epithelial cells and suggest the usefulness of the model in uncovering specific derangements during breast cancer progression. © 2002 Wiley‐Liss, Inc.
Association between a glutathione S‐transferase A1 promoter polymorphism and survival after breast cancer treatment
Authors: Sweeney Carol , Ambrosone Christine B. , Joseph Lija , Stone Angie , Hutchins Laura F. , Kadlubar Fred F. , Coles Brian F. 
Published: January 2003

AbstractGlutathione S‐transferase (GST) enzymes detoxify chemotherapeutic drugs, and several studies have reported differences in survival for cancer patients who have variant genotypes for GSTP1, GSTM1 or GSTT1 enzymes. A recently described polymorphism alters hepatic expression of GSTA1, a GST with high activity in glutathione conjugation of metabolites of cyclophosphamide (CP). To consider the possible influence of the reduced‐expression GSTA1*B allele on cancer patient survival, we have conducted a pilot study of breast cancer patients treated with CP‐containing combination chemotherapy. GSTA1 genotype was determined by polymerase chain reaction and restriction fragment length polymorphism. Kaplan‐Meier methods and Cox proportional hazards models were used to evaluate survival in relation to genotype. Among 245 subjects, 35% were GSTA1*A/*A, 49% GSTA1*A/*B and 16% GSTA1*B/*B; the genotype distribution did not differ by ethnic group, age or stage at diagnosis. Among patients who had 0 or 1 GSTA1*B allele, the proportion surviving at 5 years was 0.66 (95% CI = 0.59–0.72), whereas for GSTA1*B/*B subjects the proportion was higher, 0.86 (95% CI = 0.67–0.95). Significantly reduced hazard of death was observed for GSTA1*B/*B subjects during the first 5 years after diagnosis, hazard ratio (HR) = 0.3, 95% CI = 0.1–0.8. The association varied with time, with no survival difference observed for subjects who survived beyond 5 years. These results, although based on a small study population, describe an apparent difference in survival after treatment for breast cancer according to GSTA1 genotype. Further studies should consider the possible association between the novel GSTA1*B variant and outcomes of cancer therapy. © 2002 Wiley‐Liss, Inc.
Matrix metalloproteinase‐19 is expressed by proliferating epithelium but disappears with neoplastic dedifferentiation
Authors: Impola Ulla , Toriseva Mervi , Suomela Sari , Jeskanen Leila , Hieta Niina , Jahkola Tiina , Grenman Reidar , Kähäri Veli‐Matti , Saarialho‐Kere Ulpu 
Published: January 2003

AbstractMMP‐19 (also designated RASI) is a recently discovered member of a large family of zinc‐dependent proteolytic enzymes, most of which have been implicated in cancer growth and metastasis. It differs from the others by its chromosomal location and structure and is expressed by endothelial and vascular smooth muscle cells in vivo. Our aim was to study the putative role of MMP‐19 in skin cancer. We also examined its regulation in keratinocyte cultures using quantitative TaqMan RT‐PCR. Our results show that MMP‐19 can also be detected in stimulated keratinocytes by Northern and Western analyses. In wounds, it was found in keratinocytes outside the migrating area, while in BCC and SCC, it was present in the hyperproliferative (p63‐positive), E‐cadherin‐negative epidermis at the tumor surface but downregulated in invasive cancer islands. Expression was also evident in endothelial cells of neoangiogenic regions and in occasional stromal fibroblasts. Of the 12 tested cytokines/growth factors, only TNF‐α and PMA were able to stimulate the expression of MMP‐19 mRNA in primary keratinocytes. No MMP‐19 mRNA was detected by Northern analysis in cultured HaCaT or A5 cells or in an SCC cell line established from head‐and‐neck cancer. Our data suggest that, unlike most MMPs, MMP‐19 expression in the epidermis is downregulated during transformation and histologic dedifferentiation. © 2002 Wiley‐Liss, Inc.
Association of genomic imbalances with drug resistance and thermoresistance in human gastric carcinoma cells
Authors: Tönnies Holger , Poland Julia , Sinha Pranav , Lage Hermann 
Published: January 2003

AbstractTherapy resistance is the major obstacle to advances in successful cancer treatment. To characterize chromosomal alterations associated with different types of acquired MDR and thermoresistance, we applied CGH to compare a unique panel of human gastric carcinoma cells consisting of the parental, drug‐sensitive and thermosensitive cancer cell line EPG85‐257P, the atypical MDR variant EPG85‐257RNOV, the classical MDR subline EPG85‐257RDB and their thermoresistant counterparts EPG85‐257P‐TR, EPG85‐257RNOV‐TR and EPG85‐257RDB‐TR. CGH with genomic DNA prepared from these cell lines as probes successfully identified genomic gains and/or losses in chromosomal regions encoding putative genes associated with drug resistance and/or thermoresistance. These genes included various members of the families of ABC transporters and molecular chaperones. The importance of these cell variant‐specific genomic imbalances in the development of MDR and thermoresistance is discussed and remains to be elucidated. © 2002 Wiley‐Liss, Inc.
Complete loss of HLA class I antigen expression on melanoma cells: A result of successive mutational events
Authors: Paschen Annette , Méndez Rosa María , Jimenez Pilar , Sucker Antje , Ruiz‐Cabello Francisco , Song Mingxia , Garrido Federico , Schadendorf Dirk 
Published: January 2003

AbstractAlterations in the surface expression of HLA class I molecules have been described as a strategy of tumors to evade recognition by cytotoxic T cells. We detected complete loss of HLA class I antigen presentation for 2 tumor cell lines from 1 melanoma patient, the first originated from a regional lymph node lesion diagnosed simultaneously with the primary tumor and the second established 8 months later from a metastatic pleural effusion sample. Antigen presentation was not inducible with IFN‐γ but could be restored after transfection of tumor cells with b2m cDNA, indicating a defect in b2m expression. Analysis of the nature of this defect revealed that it originated from at least 2 mutational events affecting both copies of the b2m gene: a microdeletion of 498 bp in one b2m gene, including its entire exon 1, and a macrodeletion involving the entire copy of the second b2m gene. Microsatellite analysis pointed to the macrodeletion by demonstrating LOH for several specific markers on the long arm (q) of chromosome 15. Structural imbalance of 15q was verified by FISH. FISH studies also indicated the coexistence of a structurally abnormal variant of chromosome 15q with 2 apparently entire chromosomes 15q harboring the homozygous b2m microdeletion. Block of b2m expression in tumor cells builds a barrier to immunotherapy of cancer patients, and its early incidence should be of major consideration in the development and design of immunotherapeutic strategies. © 2002 Wiley‐Liss, Inc.
Porous titanium‐nickel for intervertebral fusion in a sheep model: Part 1. Histomorphometric and radiological analysis1
Authors: Assad Michel , Jarzem Peter , Leroux Michel A. , Coillard Christine , Chernyshov Alexandr V. , Charette Sylvie , Rivard Charles‐H. 
Published: January 2003

AbstractPorous titanium‐nickel (PTN) implants represent an alternative to traditional intervertebral fusion cages. Indeed, PTN materials possess interconnecting pores with cell capillarity properties that may promote bone ingrowth and intervertebral fusion without the need for bone grafting. In this study, a PTN intervertebral fusion device was compared to a conventional TiAlV cage packed with autologous bone in a sheep model. The two devices were implanted at two noncontiguous intervertebral lumbar sites for 3, 6, and 12 months. PTN osseointegration showed a time‐dependent trend increasing from 21.4% to 37.6% (3–12 months), whereas TiAlV cages remained at the same level of bone ingrowth (22.7%–25.4%; 3–12 months). Furthermore, PTN bone apposition (10.9%–24.2%; 3–12 months) was significantly higher than that of TiAlV implants (1.1%–5.1%; 3–12 months; p < 0.001, ANOVA). Radiological fusion scores increased with postsurgery time regardless of material type, but were consistently superior for PTN (12.5–18.5; 3–12 months) than for TiAlV cages (2.0–15.0; 3–12 months; p < 0.001, ANOVA). Implant materials were not significantly different according to the radiological interbody index based on preoperative disc height: Interbody index began at 132.6% (PTN) and 123.5% (TiAlV) immediately after surgery, then declined to 80.8% (PTN) and 91.0% (TiAlV) after 12 months. Nevertheless, ungrafted PTN constituted an excellent substrate for osteogenic cell integration and represents a new osteoconductive biomaterial with improved fusion characteristics in comparison to conventional TiAlV cages. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 64B: 107–120, 2003
Surface composition analysis of failed cementless CoCr‐ and Ti‐base‐alloy total hip implants
Authors: Decking R. , Reuter P. , Hüttner M. , Puhl W. , Claes L. E. , Scharf H. P. 
Published: January 2003

AbstractThe surfaces of retrieved failed cementless total hip implants made of cobalt‐chromium‐molybdenum casting alloy and of wrought titanium 6‐aluminum 4‐vanadium alloy were studied with the use of scanning‐electron microscopy (SEM), energy‐dispersive X‐ray analysis (EDX) and X‐ray photoelectron spectroscopy (XPS). New implants of the same make served as controls. The XPS scans revealed a dense carbon layer on the entire analyzed specimen. The relative composition of the titanium alloy implants showed an overall agreement with the international standards for implants for surgery, and the overall surface composition did not change over the period of the implantation. However, an inhomogeneous distribution of the constituents could be demonstrated in the retrieved as well as in the new MEC‐screw rings made of TiAl6V4 alloy, an implant that has been linked to a high early failure rate. In the CoCr‐alloy components (Lord‐screw rings) a high percentage of aluminum, mainly organized in aluminum inclusions, was found in the retrieved as well as in the new implants. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 64B: 99–106, 2003
Construction of a high efficiency retroviral vector for gene therapy of Hunter's syndrome
Authors: Hong Youngtae , Yu Seung Shin , Kim Jong‐Mook , Lee Karim , Na Young Soon , Whitley Chester B. , Sugimoto Yoshikazu , Kim Sunyoung 
Published: January 2003

AbstractBackgroundAs an alternative method to the conventional therapies for Hunter's syndrome, which is a lethal lysosomal storage disorder, we have developed gene delivery vehicles using a series of retroviral vectors. The objective of this study was to develop a safe and efficient retroviral vector and to optimize conditions for efficient transduction of human bone marrow CD34+ stem cells using our vector.MethodsWe constructed three types of MLV‐based retroviral vectors expressing iduronate‐2‐sulfatase (IDS) which is deficient in patients suffering from Hunter's syndrome: MIN‐IDS and MIM‐IDS, which express IDS along with bacterial neo and human MDR genes, respectively, and MT‐IDS lacking any selectable marker. Respective producer lines were derived from the packaging line, PG13, and compared for viral titer and levels of gene expression. After comparing, the retroviral vector, MT‐IDS, was used to transduce human bone marrow CD34+ stem cells on fibronectin under various MOIs.ResultsIn comparison, MT‐IDS not only produced the highest viral titer (close to 107 cfu/ml), but also showed the highest level of gene expression in various transduction assays and RNA analysis. When 1.5 × 105 human CD34+ bone marrow cells were transduced with MT‐IDS under the most optimal MOIs, about 80% of total colony forming units were shown to contain the IDS cDNA.ConclusionsMinimum‐sized retroviral vector that contains no selective marker as well as a viral coding sequences could drive a high level of gene expression, be produced efficiently from the producer line, and enter hematopoietic cells at a high frequency. Our data suggest the great potential for using MT‐based vector(s) in a gene therapy trial for Hunter's syndrome utilizing human CD34+ stem cells as target cells. Copyright © 2002 John Wiley & Sons, Ltd.
Gene therapy for prostate cancer using the cytosine deaminase/uracil phosphoribosyltransferase suicide system
Authors: Miyagi Tohru , Koshida Kiyoshi , Hori Osamu , Konaka Hiroyuki , Katoh Hiroaki , Kitagawa Yasuhide , Mizokami Atsushi , Egawa Masayuki , Ogawa Satoshi , Hamada Hirohumi , Namiki Mikio 
Published: January 2003

AbstractBackgroundCytosine deaminase (CD) activates prodrug 5‐FC to 5‐FU and is used for suicide gene therapy (the CD/5‐FC system). E. coli uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that directly converts 5‐FU into 5‐fluorouridine monophosphate and improves the antitumoral effect of 5‐FU. This study demonstrates the effectiveness of transduction of the UPRT gene in addition to CD/5‐FC cancer suicide gene therapy.MethodsWe investigated a combined suicide gene transduction therapy for human hormone independent prostate cancer cell line DU145 using two separate adenovirus vectors expressing the E. coli CD and E. coli UPRT genes and systemic 5‐FC administration (the CD+UPRT/5‐FC system).ResultsCells transfected with AdCA‐UPRT showed approximately 57 times lower IC50 to 5‐FU compared with those transfected with AdCA‐LacZ. Furthermore, cells transfected with AdCA‐CD and AdCA‐UPRT proved to be more sensitive to 5‐FC compared with those transfected with AdCA‐CD. Intratumoral injection of AdCA‐CD and AdCA‐UPRT drastically suppressed the growth of tumors which had generated from DU145 cells inoculated into athymic (nude) mice compared with those injected with AdCA‐LacZ or AdCA‐LacZ and AdCA‐CD.ConclusionsThese results suggest that the CD+UPRT/5‐FC system could be a powerful factor in human prostate cancer suicide gene therapy. Copyright © 2002 John Wiley & Sons, Ltd.
Optimisation of dendrimer‐mediated gene transfer by anionic oligomers
Authors: Maksimenko Andrei V. , Mandrouguine Vasilii , Gottikh Marina B. , Bertrand Jean‐Remi , Majoral Jean‐Pierre , Malvy Claude 
Published: January 2003

AbstractBackgroundThe application of synthetic vectors for gene transfer has potential advantages over virus‐based systems. Their use, however, is limited since they generally lack the efficiency of gene transfer achieved with recombinant viral vectors such as adenovirus. Polyamidoamine (PAMAM) and phosphorus‐containing dendrimers (P‐dendrimers) are specific polymers with a defined spherical structure. They bind to DNA through electrostatic interactions thus forming complexes that efficiently transfect cells in vitro.Methods and resultsThe influence of anionic oligomers (oligonucleotides, dextran sulfate) on dendrimer‐mediated polyfection of cultured cells has been studied. Anionic oligomers have been found to increase significantly the capacity of the PAMAM and P‐dendrimers for DNA delivery into cells when they were mixed with plasmid DNA before addition of dendrimers. The efficiency of the DNA/dendrimer penetration depends on the size, structure and charge of anionic oligomers.ConclusionsOur results represent an important step towards the optimisation of gene transfer mediated by two types of dendrimers. The use of anionic oligomers improves the efficiency of gene expression within cells. As a consequence, a very efficient cell polyfection can be achieved with a lower plasmid quantity for the PAMAM dendrimer greatly increasing the gene expression level for P‐dendrimers. Copyright © 2002 John Wiley & Sons, Ltd.