bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of multifield three‐dimensional conformal radiotherapy of lung cancer using a total lung dose/volume histogram
Authors: Greenberger Joel S. , Kalend Andre , Sciurba Frank , Jett James R. , Landreneau Rodney , Belani Chandra 
Published: February 2007

AbstractA measurable improvement in the efficacy of the three‐dimensional radiotherapy (RT) of primary lung cancer patients with unresectable disease will require the development of a technique that increases the therapeutic ratio of dose delivered to the tumor volume relative to functional lung. A full course of definitive RT dose was delivered to six consecutive primary lung cancer patients using multiple fields with treatment portals tightly conformed to the tumor shape in beams‐eye‐view, using multileaf collimation. For each patient, a treatment planning dose/volume histogram (DVH) was constructed considering the most anatomically normal tissues in both the ipsilateral and contralateral lungs. When compared to a standard anteroposterior‐posteroanterior (AP‐PA) treatment plan followed by parallel‐opposed oblique fields with conventional blocks, the five‐field conformal technique yielded a significantly lower integral lung dose as determined by cumulative DVH data. We compared the data for total lung capacity in cubic centimeters from the treatment planning DVH with that obtained by pulmonary function tests and found good concordance. The present RT technique and patient evaluation program should provide a valuable approach toward improving the quality of life in irradiated lung cancer patients, and may also guide efforts by which to escalate the dose to a tumor volume in the chest. © 1995 Wiley‐Liss, Inc.
Mechanisms of escaping cellular senescence
Authors: Shay Jerry W. , Wright Woodring E. 
Published: February 2007

AbstractThe two‐stage model of cellular senescence, M1 (mortality stage 1) and M2 (mortality stage 2), represents independent mechanisms limiting the proliferative capacity of normal somatic cells. The cellular proteins p53 and either pRB or an RB‐like activity appear to be important in the inhibition of cell proliferation that occurs when the M1 mechanism is activated. Because telomeres (the ends of chromosomes) shorten progressively with each cell division in normal somatic cells, it has been proposed that telomere attrition is the molecular measure (clock) of the proliferative potential remaining in cells. However, the M1 mechanism is activated when there are several kilobases of telomeric repeats left; thus, presently, it is not understood how or if telomere shortening controls the onset of the M1 mechanism. In the presence of viral oncogenes or somatic mutations that block cellular senescence, cells divide beyond M1 (extension of life span), and telomere erosion continues. This process persists until a second independent mechanism, M2, is activated, again resulting in inhibition of cell proliferation. The M2 mechanism may result from terminal telomere shortening, when there are so few telomeric repeats remaining that cells either stop dividing or die. In tumor‐derived cell lines, telomeres do not continue to shorten and are maintained by the ribonucleoprotein enzyme telomerase. In almost all normal human somatic cells, telomerase activity is repressed. A hypothesis that is gaining momentum is that a rare cell escapes M2 by inactivating the pathway repressing telomerase. The reactivation of telomerase may be a necessary event for the sustained growth of most human tumors. © 1995 Wiley‐Liss, Inc.
Immortalization of cultured human fibroblasts with the mutant p53 gene and X‐rays
Authors: Namba M. , Mihara K. , Kondo T. , Inoue Y. , Tsuji T. , Fushimi K. , Shima T. , Iijima M. 
Published: February 2007

AbstractThe mutant p53 gene (mp53; codon 273Arg‐His) was introduced into normal human fibroblasts (OUMS‐24 strain), and a G418‐resistant clone, OUMS‐24/P6, was obtained. This clone expressed mp53 and showed an extended life span, but it senesced at the 79th population‐doubling level (PDL). When these cells were subjected to eight intermittent treatments with 2 Gy of x‐rays, they were immortalized, whereas normal fibroblasts (OUMS‐24) into which mp53 had not been introduced were not immortalized by the same x‐ray treatment. These results indicate that the introduction of mp53 alone is not sufficient for immortalization of human cells and that mutations of the remaining wild‐type p53 or other genes are also necessary. © 1995 Wiley‐Liss, Inc.
Genetic changes during immortalization of human cells
Authors: Reddel Roger R. , Bryan Tracy M. , Rogan Eileen M. , Noble Jane R. , Maclean Kenneth , Whitaker Noel J. , Chang Andy C.‐M. 
Published: February 2007

AbstractSpontaneous immortalization of fibroblasts containing an inherited mutation of one p53 allele was associated with loss of the wild‐type p53 allele and loss of p16INK4 gene expression, but this combination of genetic events was insufficient for immortalization. Loss of p16INK4 expression appears to be an alternative to loss of functional retinoblastoma gene product. In all cell lines studied, immortalization was associated either with stabilization of telomere length in the presence of telomerase activity or with the acquisition of long and heterogeneous telomeres in the absence of detectable telomerase. The role of other genes, such as human stanniocalcin, in the immortalization process is under investigation. © 1995 Wiley‐Liss, Inc.
Human prostate epithelial cell model system for carcinogenic studies
Authors: Kuettel Michael , Jung Mira , Thraves Peter , Prasad Sarada , Varghese Susan , Rhim Johng , Dritschilo Anatoly 
Published: February 2007

AbstractThe immortal human prostate cell line, 267B1, has been used as a model system for investigating molecular events in carcinogenesis. Exposure of these cells to ionizing radiation results in progression to anchorage‐independent growth. In addition, transfection of 267B1 cells with the activated Ki‐ras oncogene results in tumorigenicity.We present here the further characterization of these cells, observing that both the immortalized 267B1 cell line and irradiated clones contain the wild type Ki‐ras‐2 gene and a Ki‐ras pseudogene (Ki‐ras‐1 like). No mutations in p53 were observed. Cells expressing anchorage‐independent growth following x‐ray irradiation exhibited loss or rearrangements in numerous chromosomes, including chromosomes 10 and 18. These data are important for investigators using this model cell system for studies of carcinogenesis, gene expression, and signal transduction. © 1995 Wiley‐Liss, Inc.
Effects of selenium on glutathione peroxidase activity and radioprotection in mammalian cells
Authors: Diamond Alan M. , Murray Judith L. , Dale Phylis , Tritz Richard , Sandstrom Paul A. , Grdina David J. 
Published: February 2007

AbstractThe media of representative mammalian cell lines were supplemented with low levels of selenium in the form of sodium selenite in order to investigate the effects of selenium on mammalian cells. Following incubation in 30 nM sodium selenite, these cells were assayed for changes in glutathione peroxidase (GPx) activity. The cells examined included NTH 3T3 mouse fibroblasts, PC 12 rat sympathetic precursor cells, SupT‐1 human lymphocytes, MCF‐7adr human breast carcinoma cells, and AA8 Chinese hamster ovary (CHO) cells. Selenium supplementation resulted in a marginal increase in GPx activity for the NIH 3T3, MCF‐7adr, and Supt‐1 cells but stimulated GPx activity approximately fivefold in PC 12 and AA8 cells. AA8 cells were selected to evaluate whether selenium supplementation was radioprotective against 60cobalt gamma irradiation. Protection against radiation‐induced mutation was measured by evaluating mutation frequency at the hprt locus. In this assay, preincubation of AA8 CHO cells significantly protected these cells from exposure to 8 Gy. © 1995 Wiley‐Liss, Inc.
Molecular and genetic characterization of human keratinocytes transformed with ionizing radiation
Authors: Thraves Peter J. , Varghese Susan , Jung Mira , Prasad Sarada C. , Rhim Johng S. , Dritschilo Anatoly 
Published: February 2007

AbstractThe molecular mechanisms which underlie the biological effects of exposure to ionizing radiation have particular relevance to radiation protection and risk assessment since most cancers are of epithelial origin. It is important to obtain a better understanding of radiation‐induced oncogenic transformation in this cell type. Our previous studies have demonstrated that both X‐rays and fission neutrons can transform immortalized human epidermal keratinocytes to a malignant phenotype. In both studies, exposure to ionizing radiation led to the development of morphologically altered cells and focus formation at confluence. These radiation‐transformed cultures grew with an increased saturation density, exhibited anchorage‐independent growth, and formed tumors in athymic mice. These radiation studies have been expanded to include a molecular analysis of the cellular ras genes and the tumor suppressor gene p53. Single‐strand conformational polymorphism (SSCP) analysis and DNA sequencing demonstrated the absence of point mutations, deletions, and rearrangements in codons 12/13 and 61 in the Ha‐ras, Ki‐ras, or N‐ras genes and exons 2–11 of the p53 tumor suppressor gene. Karyotypic analysis of these human keratinocytes indicated a loss of heterozygosity at the tumor suppressor loci RBI, DCC, APC, MTS1, and WT1 upon immortalization. Furthermore, karyotypic analysis of the X‐ray‐treated keratinocytes in relation to their tumorigenic potential indicated that the development of malignancy was associated with a duplication of material on chromosome 11 between regions q14 and q22. This additional material on chromosome 11 at q14/q22 was observed in all of the irradiated tumorigenic keratinocytes. A similar tandem duplication of the 11q13>q23 region has been observed in malignant lesions of oral squamous cell carcinoma and in head and neck tumors. Deletions in the same region were also observed in the irradiated non‐tumorigenic cells. Together, these observations indicate that this region of chromosome 11 contains gene (s) with a role in tumorigenicity and that the duplication observed in chromosome 11 may be the primary event leading to radiation‐induced transformation of these immortalized human keratinocytes. These studies demonstrate that mutations in either the cellular p53 or ras genes do not occur in these immortalized human epithelial cells (RHEK‐1) when transformed to a malignant phenotype with ionizing radiation. Furthermore, specific regions on chromosome 11 may be a target for the transforming effects of ionizing radiation. © 1995 Wiley‐Liss, Inc.
Radon‐induced neoplastic transformation of human bronchial epithelial cells
Authors: Hei Tom K. , Piao Chang Q. , Han Edward , Sutter Thomas , Willey James C. 
Published: February 2007

AbstractEpidemiological studies have shown that inhalation of radon is associated with an increased risk for lung cancer among underground miners. The cellular and molecular mechanisms for radon‐induced carcinogenesis are not clear. By using a human papillomavirus‐immortalized human bronchial epithelial cell line, we show here that a single 30 cGy dose of these high‐energy particles induced tumorigenic conversion of the cells 3–4 months postirradiation at frequencies estimated to be ∼4 × 10−7. Transformed cells arise through a series of sequential steps, including altered growth kinetics, loss of response to serum‐induced terminal differentiation, anchorage‐independent growth, and rumorigenesis, with each preceding stage representing a necessary yet insufficient step toward the later, more malignant phase. Northern and Western blot analyses showed overexpression of the G1 cell‐cycle‐control kinase, cyclin D1. Analysis of genomic DNA from the tumorigenic cell lines using polymerase chain reaction amplification and restriction enzyme analysis demonstrated no mutation in the K‐ras oncogene, which has frequently been found to be mutated in human lung cancers. Western blot analysis showed that both control BEP2D cells and their tumorigenic variants contained phosphorylated Rb proteins. This model provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells. © 1995 Wiley‐Liss, Inc.
Individual variation in the expression of proteins involved in the regulation of growth and apoptosis post‐DNA damage in normal human urothelium
Authors: Mothersill C. , Colucci S. , Arrand J. , Gamble S. , Harney J. V. , Murphy D. M. , Seymour C. B. 
Published: February 2007

AbstractThe changes in expression of five oncoproteins involved in the regulation of repair of DNA damage and postdamage proliferation of cells were measured in cultures of normal urothelium from over 60 patients. The results for oncoprotein expression were correlated with apoptotic index and growth rate postexposure. Both radiation and a metabolite of nitrosamine found in urine led to increased levels of p53 in cultured urothelium. There was significant interpatient variation. PCR‐SSCPE (single strand conformational polymorphism electrophoresis) analysis of foci occurring in the exposed cultures showed multiple mobility shifts in exons 5–8 of the p53 gene. These were present in irradiated cultures at high frequency, but they were only present in two of six cultures exposed to nitrosamine. Cells surrounding foci, although they were p53+ by immunocytochemistry, were mainly negative for mutations using SSCPE analysis. Expression of bcl‐2 was significantly increased following radiation exposure, but it was unchanged following nitrosamine treatment. EGFr and p21ras were uniformly increased in all carcinogen‐exposed cultures The results suggest that an early breakdown in control mechanisms of growth arrest and apoptosis may occur in urothelium following carcinogen exposure. The problem of interindividual variation in response must be considered in studies of this sort. © 1995 Wiley‐Liss, Inc.
Mini review: Molecular basis of breast cell transformation
Authors: Russo J. , Barnabas N. , Zhang P. L. , Adesina K. 
Published: February 2007

AbstractIn order to determine what is the role of genomic alterations in neoplasia, it is necessary to verify what is their function at each one of the various stages of breast cancer progression, which initiates as ductal hyperplasia, progressing to atypical ductal hyperplasia, carcinoma in situ, and invasive and metastatic adenocarcinoma. These studies are hindered by the fact that these stages are not always present in a single patient, or in a sequential manner, or when present the available material might be insufficient or inadequate for performing genetic manipulation for testing their functional role. These disadvantages have been overcome by utilizing an in vitro model of cell transformation, the spontaneously immortalized human breast epithelial cell line (HBEC) MCF‐ 10F, which upon treatment with the chemical carcinogens benzo(a)pyrene (BP) or 7,12‐dimethyl‐benz(a)anthracene (DMBA) expresses in a sequential fashion all the phenotypes indicative of neoplastic transformation, i.e., increased survival in agar, formation of colonies in agar methocel, invasiveness in a matrigel in vitro system, and tumorigenesis in severe combined immunodeficient (SCID) mice. The immortalization of MCF‐1 OF cells is associated with the presence of a point mutation in exon 7 of the tumor suppressor gene p53. Carcinogen‐induced transformation was manifested as colony formation in agar methocel and anchorage independence, which were associated with loss of heterozygosity (LOH) and point mutations in codons 12 and 61 of c‐Ha‐ras gene. Other oncogenes involved in this early stage were c‐neu, c‐myc, and int‐2. The expression of the tumorigenic phenotype was associated with LOH in the telomeric portion of chromosome 17 and overexpression of the mdm2 gene. This in vitro system provides all of the sequential steps to neoplastic transformation in a reproducible manner, thus providing a paradigm for clarifying the role of the genetic alterations in tumor initiation and progression. © 1995 Wiley‐Liss, Inc.
Extended abstract: Chromosome rearrangements involved in transformation of human T‐Cell leukemia virus type I infected human lymphocytes
Authors: Mochizuki Shigenobu , Kawamura Kiyoko , Maruyama Koshi 
Published: February 2007

AbstractFollowing human T‐cell leukemia virus type I (HTLV‐I) infection, human lymphocytes (Coculture‐5) acquired capacity to grow continuously in the presence of cytokine. Coculture‐5 cells transformed (UV‐1) following ultraviolet (UV) irradiation. Coculture‐5 and UV‐1 cells had abnormalities of chromosomes 1 and 7. Coculture‐5 cells also transformed (Coculture‐15) following cocultivation with UV‐1 cells. In Coculture‐15, 18 structural abnormalities were observed. Of these, 6 were of chromosome 1 and 5 were of chromosome 7. The marker chromosome of UV‐1 cells, i(7q), was seen in up to 80% of Coculture‐15 cells. All UV‐1 cells examined had i(7q) with single centromeric G‐band, whereas 60% of Coculture‐15 cells had i(7q) with double centromeric G‐bands. By fluorescence in situ hybridization (FISH), an alpha satellite centromeric DNA probe for chromosome 7 gave a single band in i(7q) in UV‐1 and single or double bands in i(7q) in Coculture‐15 cells. These findings suggest that integration of HTLV‐I proviral DNA into chromosomal DNA causes fragility of certain chromosomes of infected cells and leads them to transformation. © 1995 Wiley‐Liss, Inc.
Adaptation of the Reservoir Fish Assemblage Index (RFAI) for assessing the Barra Bonita Reservoir (São Paulo, Brazil)
Authors: Petesse M. L. , Petrere M. , Spigolon R. J. 
Published: February 2007

AbstractIn order to evaluate the environmental condition of the Barra Bonita Reservoir, we adapted the Index of Biotic Integrity (IBI). We chose 24 sampling sites in which three types of habitats were sampled: the mouths of tributaries, the central reservoir and the lateral reservoir. Fish were caught in two seasons (dry and rainy) using 10 gillnet gangs, with meshes ranging from 3 to 12 cm between opposite knots, and funnel traps. Abiotic and biotic variables were measured. Due to the artificial nature of the reservoir, the term biotic integrity was considered inappropriate and the term RFAI (Reservoir Fish Assemblage Index) was adopted. Twelve metrics from sixteen possibles were selected using the Pearson correlation coefficient. The reference conditions were set up based on the criteria of the best condition observed. For each metric, a score of 1, 3 or 5 was assigned as it strongly departs (1), slightly departs (3) or approaches (5) the reference condition. The index value is the sum of the metrics partial scores and ranges from 12 to 60. To evaluate the importance of the unit of measurement of the metric, the index was calculated in fish number (RFAIN) and in weight (RFAIW). The correlation between RFAIN and RFAIW was very high (r = 0.90, n = 46) indicating that the unit of measurement does not influence the final result of the index. Most of the sampling sites were classified in the ‘reasonable’ RFAI category. Only the central sites were classified as ‘poor’. To validate the RFAI, another index, the Habitat Quality Index (HQI), was built starting from the physiochemical and habitat variables collected. The correlation of the RFAI with the HQI was highly significant (RFAIN, r = 0.37; RFAIW, r = 0.47; n = 46), indicating that they respond in the same way to environmental degradation. The HQI metrics which most affect RFAI were depth, surrounding landscape and macrophyte presence/absence. Copyright © 2007 John Wiley & Sons, Ltd.
Do fish locks have potential in tropical rivers?
Authors: Stuart Ivor G. , Berghuis Andrew P. , Long Peter E. , Mallen‐Cooper Martin 
Published: February 2007

AbstractThis study evaluated attraction and passage of native fish through an automated fish lock on the tropical Fitzroy River in north‐eastern Australia. In 69 samples (24 h each) taken at the exit and entrance of the fish lock, 17 fish species and 13 402 individuals were collected, at a maximum rate of 3317 fish per day. During low river flows, the fish lock transferred a broad size range of fish (35–710 mm long), though migratory biomass was small. Removal of a vertical fish‐crowding device did not affect the passage rate. Netting studies and observations of fish migrating below the weir suggested that the entrance was poorly located during high flows and another fishway near the spillway would enhance fish passage. The fish lock was inoperative for 48% of the time, due to mechanical and software failure, and a narrow operational range unsuited to the variable hydrology. Nevertheless, these design issues are site specific and reflect that fish lock technology is in its infancy in Australia. The operational reliability of the fish lock is now greatly improved but further work is needed to optimize the automatic cycling. To accommodate the inherently variable hydrology of lowland tropical/sub‐tropical rivers into fishway design, we highlight important research needs for fishways and migratory fish communities. Fish locks are often considered a less favourable fish passage option but with the operational reliability issues partially resolved, they appear to have considerable potential for tropical river systems with low minimum flows and low biomass; with further research and design, they may have wider application. Copyright © 2007 John Wiley & Sons, Ltd.
Market analysis for the next‐generation mobile communications (DMB) service from the perspective of innovation adoption and diffusion
Authors: Sawng Yeong‐Wha , Han Hyun‐Soo 
Published: February 2007

AbstractThis study examines market acceptance for the satellite digital multimedia broadcasting (DMB) service, one of the touted new business models in Korea's next‐generation mobile communications service market, using adoption and diffusion of innovation as the theoretical framework. Market acceptance for the satellite DMB service was assessed by predicting the demand of the service using the Bass model, and the demand variability over time was then analysed by combining the innovation adoption model proposed by Rogers (Diffusion of Innovations (5th edn). The Free Press: New York, 2003). In our estimation of the Bass model, we derived the coefficient of innovation and the coefficient of imitation using actual diffusion data from the mobile telephone service market. We also reorganized the demand data along the diffusion timeline according to Rogers' innovation adoption model, using the responses by survey subjects concerning their respective projected time of adoption. The demand prediction model revealed that diffusion for both took place forming a classical S‐curve. Concerning variability in demand for the satellite DMB service, our findings, much in agreement with Rogers' view, indicated that demand was highly variable over time and depending on the adopter group. This study, as an attempt to measure the market acceptance for the satellite DMB service, a leading next‐generation mobile communications service product, stands out from related studies in that it estimates the nature and level of acceptance for specific customer categories, using theories of innovation adoption and diffusion and survey results conducted through one‐to‐one interviews. The findings and theoretical application procedures provide practical insights into further research on market analysis of new mobile communications service‐related products. Copyright © 2007 John Wiley & Sons, Ltd.