bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the results of postoperative radiotherapy for esophageal cancer
Authors: Sakata Koh‐Ichi , Aoki Yukimasa , Karasawa Katsuyuki , Nakagawa Keiichi , Hasezawa Kenji , Muta Nobuharu , Terahara Atsuro , Onogi Yuzo , Sasaki Yasuhito , Akanuma Atsuo
Published: February 2007

Ninety patients with previously untreated squamous cell carcinoma of the thoracic esophagus were treated with surgery and postoperative radiation therapy (RT) at the University of Tokyo between January 1982 and December 1992. Total dose was 50 Gy/5 weeks. The overall 5‐year survival rate was 19.7%. Sex, age, tumor site, tumor length, depth of tumor invasion, degree of lymph node metastasis, number of lymph node metastases, presence of macroscopic or microscopic residual tumor, and use of chemotherapy were analyzed for prognostic significance for survival by multivariate analysis. Tumor site (P <0.01) and number of lymph node metastases (P <0.01) were significant prognostic factors for survival of patients with esophageal carcinoma who underwent postoperative RT. Depth of tumor invasion (P< 0.09) and presence of macroscopic or microscopic residual tumor (P< 0.1) were marginally significant. The 2‐year and 5‐year survival rates were 50.0% and 0% in upper thoracic esophageal cancer, 54.5% and 21.3% in middle thoracic esophageal cancer, and 52.1% and 36.1% in lower thoracic esophageal cancer. The 5‐year survival rate was 41.1% in pT1, 50.0% in pT2, 10.5% in pT3, and 0% in pT4. The 5‐year survival rate was 30.6% in those with no lymph nodes involved, 35.8% in those with 1–3 lymph nodes involved, 27.3% in those with 4–7 lymph nodes involved, and 7.1 % in those with 8 or more lymph nodes involved. The 2‐year survival rate was 15.0% for patients who had macroscopic residual tumor, 33.3% for patients whose surgical margins were microscopically involved, and 57.7% for patients whose surgical margins were free of tumor. Careful histological examination of the resected specimen will identify patients most likely to benefit from postoperative RT. Data from this non‐randomized series suggest that postoperative RT improves survival in cases with pT2 or pN1. © 1995 Wiley‐Liss, Inc.
Effect of BW12C on mouse tumor response to radiation
Authors: Hendrikse A. , Blekkenhorst G. , Hering E. , Mohamed F.
Published: February 2007

The substituted benzaldehyde BW12C has previously been shown to decrease tumor oxygenation. This, in turn, was linked to the drug's ability to alter the affinity of hemoglobin for oxygen and/or to change tumor blood flow. In the present study, the ability of BW12C to modify oxygen‐hemoglobin binding affinity, tumor blood flow, and tumor radiosensitivity was investigated using BALB/c mice with a 3‐methylcholanthrene‐induced rhabdomyosarcoma and WHT mice with a Fib/T tumor. Results for BALB/c mice indicated that BW12C caused an initial decrease in the P50 and in tumor blood flow, which was accompanied by a decrease in the radiosensitivity of the chemically induced rhabdomyosarcoma. When the P50 and tumor blood flow levels returned to normal again, tumor radiosensitivity increased and exceeded that of mice that were not given BW12C. Although BW12C caused a similar pattern of change in WHT mice with respect to oxygen‐hemoglobin binding affinity, the drug had no effect on Fib/T tumor blood flow or radiosensitivity. © 1995 Wiley‐Liss, Inc.
Splenic irradiation for patients with polycythemia vera
Authors: Wazer David E. , McKeough Paul , Madoc‐Jones Hywel
Published: February 2007

Seven patients with a diagnosis of polycythemia vera (PCV) with symptomatic splenomegaly received 10 courses of splenic irradiation. Patients received a total dose of 250–1,425 cGy to the whole spleen with twice‐weekly fractionation beginning with 25 cGy per fraction, gradually escalating to no more than 100 cGy per fraction. All 10 courses resulted in palliation of the symptoms of abdominal discomfort and early satiety. Greater than 50% reduction in spleen size was observed in 7 of 10 courses. The primary toxicity was a transient decrease in circulating platelets though two patients with thrombocytopenia at presentation had improvement in their platelet counts corresponding with a decrease in spleen size. These results demonstrate that splenic irradiation with low dose, twice‐weekly irradiation is an effective way to reduce spleen size and palliate symptoms in patients with PCV. © 1995 Wiley‐Liss, Inc.
Early prostate specific antigen (PSA) response predicts PSA nadir in patients with prostate cancer treated with external beam radiation
Authors: Ennis Ronald D. , Fischer Diana B. , Pcschel Richard E.
Published: February 2007

Serum prostate specific antigen (PSA) values decrease after external beam radiation (EBRT) for clinically localized prostate cancer, reaching their nadir 6–12 months after treatment. The nadir PSA value is predictive of disease‐free survival. This prospective study was initiated to evaluate whether the early response of PSA as measured by 1) the rate of PSA decrease during treatment (PSA slope) and 2) the immediate (within 1 month) post‐treatment PSA would predict the PSA nadir.

Thirty patients treated with EBRT for clinical stages A2‐C2 (T1c‐T3c) adenocarcinoma of the prostate were enrolled in this prospective study. Nine patients were subsequently excluded because they were lost to follow‐up after less than 1 year (n = 6) or their pretreatment PSA was measured by a method other than Hybritech (n = 3). Serum PSA measurements were obtained at weeks 2, 4, and 6 of treatment (n = 21) as well as immediate post‐treatment PSA at the first follow‐up 2–4 weeks after treatment (n = 17). The end‐point analyzed was whether or not the PSA nadir was ≦ 1.5 ng/ml. A linear regression model of log(PSA) vs. time (treatment week) was fit for each patient's data. The rate of decrease of PSA (PSA slope) was estimated from this regression. The PSA slope, pretreatment PSA, immediate post‐treatment PSA, stage, and grade were studied by Cox life table regression analysis to determine predictors of PSA nadir. In the Cox model, time was measured from the start of radiotherapy until PSA ≦ 1.5 ng/ml or until the last measurement for those who did not reach this level. Models combining the significant individual factors were then constructed. The minimum follow‐up is 52 weeks and the median is 66 weeks.

The PSA slope (P= 0.05) and the immediate post‐treatment PSA (P =0.02) predicted a PSA nadir ≦ 1.5 ng/ml. Pretreatment PSA approached significance (P =0.09). A model which combined pretreatment PSA and PSA slope predicted PSA nadir ≦ 1.5 ng/ml (P= 0.05) as did PSA slope combined with immediate post‐treatment PSA (P = 0.01). Within each model, PSA slope was the stronger predictor.

In conclusion, the early response of serum PSA as measured by the PSA slope and the immediate post‐treatment PSA appears to be predictive of PSA nadir in patients treated with EBRT. More patients and longer follow‐up are needed to confirm this finding and determine whether the early response predicts disease‐free survival. © 1995 Wiley‐Liss, Inc.
Use of the protein kinase C inhibitor H‐7, l‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine, as a radiosensitizer in HeLa cells
Authors: Schnell Frederick J. , Bases Robert E. , Vikram Bhadrasain , Franklin William A.
Published: February 2007

The isoquinoline sulfonamide H‐7 has been shown to delay the onset of radiation‐induced G2 arrest suggesting its possible application as a radiosensitizer. The effectiveness of H‐7 as a radiosensitizer and its toxicity in HeLa cells were evaluated. Cells were treated with either 10 or 100 μmM H‐7 and exposed to gamma radiation (0–6 Gy). H‐7 was toxic to cells at concentrations greater than 10 μM. Addition of H‐7 had no effect on the overall dose response of the HeLa cells to gamma radiation. These results suggest that the use of agents which inhibit protein kinase C activity does not necessarily result in decreased cell survival. © 1995 Wiley‐Liss, Inc.
Effect of combined chloroquine and mild hyperthermia on hybrid spheroids containing either HeLa or S91/6 mouse melanoma cells
Authors: Djordjevic Bozidar , Lange Christopher S. , Aral Isamettin A. , Rotman Marvin
Published: February 2007

We found no significant decrease in the colony forming ability (clonogenicity) of either HeLa or S91/6 melanoma cells in hybrid spheroids incubated for 24 hr at 37°C with up to 30 μM chloroquine, nor for incubations of up to 9 hr at either 37 or 41°C with 30 μM chloroquine. Incubation for 24 hr at 41°C with chloroquine caused spheroids to disintegrate. When heating was applied to hybrid spheroids intermittently for 3 hr at the beginning and at the end of a 24 hr period of incubation with 30 μM chloroquine, there was no effect on HeLa cells but there was a highly significant decrease in the clonogenicity of S91/6 melanoma cells. Short‐term treatment (3 hr) with a combination of mild hyperthermia and 30 μM chloroquine which is non‐toxic to unirradiated cells in hybrid spheroids is, nevertheless, effective in decreasing the clonogenicity of irradiated cells of both lines. A similar increase in radiation lethality [radiation potentiating factor (RPF) of about 1.6] was obtained in both HeLa and in S91/6 cells. RPFs did not change significantly after correction of survival curves for cellular multiplicity, nor were they different from those previously reported by us for these cell lines in two versions of dense suspension cultures. Since many cells from biopsies will not grow in conventional culture systems but will do so in hybrid spheroids, the finding of similar RPF values in both systems for cell lines which will grow under both conditions suggests that hybrid spheroids may be useful for radiopotentiation studies. © 1995 Wiley‐Liss, Inc.
In vitro test of the cytotoxic equivalence between pulsed dose rate and continuous low dose rate
Authors: Erickson Beth , Shadley Jeff D.
Published: February 2007

Pulsed low dose rate (PDR) irradiation is being investigated as an alternative to continuous low dose rate (CLDR) irradiation for the treatment of certain malignancies. Mathematical modeling by Brenner and Hall suggests that the two irradiation regimens will be equivalent under certain conditions. We are testing these predictions directly by using the mouse/SCC VII in vitro‐in vivo tumor model. This study involved in vitro irradiations that would not be expected to severely stress the assumptions of the mathematical model. The cytotoxicity of CLDR was compared to that for PDR regimens consisting of hourly radiation pulses of 5, 10, or 20 minutes and a 20‐minute radiation pulse every 2 hours. A total dose of 15.7 Gy of 60Co γ‐rays was delivered over the same total time for all irradiations. Confluent cultures were irradiated in low serum at room temperature to minimize the effects of cell proliferation and cell cycling. Flow cytometric analysis demonstrated that an average of ≧80% of cells were in G0/G1 phase, with ≦5% incorporating bromodeoxyuridine. Also, mitotic indices averaged <0.2%. There were no significant differences between the mean values for these cell cycle measures between CLDR and PDR or between PDR regimens. All PDR regimens showed increased cell kill relative to the CLDR, but in no case were the increases statistically significant. The increase in cell kill was by factors of 1.14–2.00, with the greatest increase in cell kill in the PDR regimen using 5‐minute pulses once per hour. The increase in cell kill, even if it was real, would not appear to be sufficient to violate the criteria for being “clinically indistinguishable,” as suggested by Brenner and Hall. Although these results generally support the modeling of Brenner and Hall, this experimental model does show increased cell killing in the PDR regimens, and this in vitro model does not stress the assumptions of the Brenner‐Hall model as severely as in vivo models would. © 1995 Wiley‐Liss, Inc.
Cisplatin‐induced enhancement of radioresponse in a murine mammary carcinoma: Test of a role for apoptosis
Authors: Wheeler James A. , Clifton Stephens L. , Milas Luka , Hunter Nancy R. , Willingham Veronica I. , Meyn Raymond E.
Published: February 2007

Programmed cell death or apoptosis has recently been recognized as an important mode of cell death in the response of tumor cells to cytotoxic treatments associated with chemotherapy or radiation therapy (RT). We previously showed that both cisplatin and radiation induced substantial apoptosis in the murine mammary tumor MCA‐4 when administered as single agents in vivo. Moreover, the levels of apoptosis correlated with tumor response measured as tumor growth delay. In the current study a role for apoptosis in a combined treatment with cisplatin and radiation was evaluated. Mice bearing MCA‐4 tumors were irradiated at different times following an injection with cisplatin, and tumor growth delay was assessed. Apoptosis was scored from histological sections of the tumors. The results showed that whereas the cisplatin sensitized the MCA‐4 tumor to a subsequent irradiation in terms of the growth delay, the apoptotic index never rose above the maximum level characteristic of either agent when used singly. Thus, there was no indication that cisplatin sensitized the tumor cells to radiation‐induced apoptosis. We conclude that apoptosis is not the only important mechanism for cell killing in tumors following cytotoxic treatment and that tumor response is a complex composite of many different factors. © 1995 Wiley‐Liss, Inc.
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

A 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

The 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

The 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

Spontaneous 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

The 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

The 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

The 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

Epidemiological 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

The 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

In 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

Following 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

In 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

This 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

This 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.
Examining the effects of stressors and resources on multiple sclerosis among African Americans and Whites
Authors: Johnson Susan K. , Terrell Debra , Sargent Carrie , Kaufman Michael
Published: February 2007

The first objective of this study was to explore whether stressors and resources, quality of life and symptom severity differed among African American and White individuals with multiple sclerosis (MS). The second aim was to examine whether social stressors and resources were related to symptom severity and overall quality of life, regardless of ethnicity. Sixteen African American and 28 White patients completed measures of stressors and resources, symptom severity and quality of life. There were no significant differences among the groups, with the exception of African Americans reporting fewer friend resources and more financial stressors than White participants. Irrespective of ethnicity, greater symptom severity was associated with a poorer quality of life, fewer financial and family resources. Financial and family resources, and positive life events were positively correlated with quality of life. The results indicate that strengthening existing familial support and reducing social stressors in MS patients could impact quality of life, regardless of ethnicity. Copyright © 2007 John Wiley & Sons, Ltd.
College student stress: the influence of interpersonal relationships on sense of coherence
Authors: Darling Carol Anderson , McWey Lenore M. , Howard Stacy N. , Olmstead Spencer B.
Published: February 2007

The purpose of this study was to investigate college student stress, how students cope with stress, and how the stress of renegotiating self and relationships influences one's sense of coherence (SOC). A survey research design was utilized incorporating 596 college students. Using family stress theory, this study examined how stress associated with relationships, level of coping, physical and emotional reactions to stress, and quality of life can be integrated to predict SOC in male and female college students. Findings indicate that female college students experience greater stress from quality of friendships, love relationships and relationships with parents. Whereas emotional health had the greatest effect on SOC for females, family relationships had the greatest effect on SOC for males. Qualitative responses were also examined, providing insight into students' perceptions of stressors. Conclusions and implications for educators, researchers and family therapists are discussed. Copyright © 2007 John Wiley & Sons, Ltd.
Critical evaluation of results of extension of indication for surgery for primary bronchogenic carcinoma
Authors: Wu Shang‐Fang , Huang Ou‐Lin , Wu Huai‐Shen , Chow Yun‐Chong , Sun Teh‐Kwui , Ron Zhong‐Bei , Cheng Wen‐Hu , Gao Cheng‐Xin , Wu Huai‐Sung , Koo Kai‐Shih
Published: February 2007

Among 3,120 surgically resected cases (1957–1983) in Shanghai Chest Hospital, 1,476 resections (47.3%) were performed under extended indication. Six categories— (1) aged 70–87 years (102), (2) associated with severe impairment of pulmonary function (25), (3) small‐ceil anaplastic type (143), (4) stage III tesion (1,145), (5) invading carina (29), (6) with disseminated pleural metastasis and effusion (32) — were critically evaluated. For the first four categories, long‐term survival rates were very encouraging, whereas only technical advancement and short‐term results were discussed for the last two. The authors present strategic points significant in availing higher overall operability and hence the overall survival rate, shedding light on the increase of curative potential for lung cancer.
Treatment of advanced cancer of the prostate
Authors: Chisholm Geoffrey D.
Published: February 2007

Advanced cancer of the prostate may be either locally advanced or distant. Staging methods available to define the extent of the disease are relatively imprecise; non‐invasive methods rely on tumour markers and radioiso‐topes; invasive methods range from fine needle aspiration to lymph node dissection. Exact definitions of criteria of response to treatment are essential to evaluate diferent forms of treatment.

Primary treatment of metastatic disease is based on hormone manipulation. Those who either never respond or relapse after primary treatment may show some response to further hormone therapy but usually require the combination of radiotherapy and analgesia to control their symptoms. The response rates to chemotherapy are disappointing.
The omentum in malignant diseases
Authors: Abbott William C. , White Harvey
Published: February 2007

The technique and applications of omentoplasty are reviewed from the point of view of the surgical oncologist, with particular emphasis on the use of the omentum in (1) gastrointestinal anastomoses, (2) covering peritoneal defects or radical intra‐abdominal operations for neoplastic disease, (3) urological complications, (4) breast cancer, (5) abdominal and chest wall resections, (6) the prevention of arterial graft erosions, and (7) the treatment of lymphoedema and chemotherapeutic burns. Complications are discussed as well as future prospects.
Registry and follow‐up systems of trophoblastic disease in Japan
Authors: Kawashima Yoshiro , Maeda Makoto , Fujii Toshiro
Published: February 2007

With recent progress in chemotherapy, the prognosis of patients with trophoblastic disease has greatly improved, but the remission rate of patients with choriocarcinoma remains unfavorable. To improve the prognosis of these patients, early detection and early treatment are essential. Under the leadership of the Committee of Trophoblastic Disease of the Japan Society of Obstetrics and Gynecology, regional registries of trophoblastic disease were started in 1974. By 1982 14 prefectures with a total population of 46,893,620 were included in the registry. The early detection and treatment and follow‐up made possible by the legistry in addition to the introduction of advanced chemotherapy may be responsible for a rapidly decreasing trend in the death rate from this disease.
Radical hysterectomy for cancer of the uterine cervix
Authors: Sekiba Kaoru
Published: February 2007

A recent modification of radical hysterectomy for cancer of the uterine cervix is described in detail. This modification of the Okabayashi operation has shown improved reliability and safety. Because of the extensive resection of supporting ligaments and loose connective tissue, bleeding may be induced and a wide operation field is necessary to prevent injury to the pelvic viscera.
Primary tumors of the heart: A review with emphasis on diagnosis and potential treatment modalities
Authors: Becker Richard C. , Loeffler Jay S. , Leopold Kenneth A. , Underwood Donald A.
Published: February 2007

Primary cardiac tumors, while uncommon, are not rare neoplasms. They occur in individuals of all ages. A variety of benign and malignant tumors has been described. Presenting signs and symptoms mimic numerous systemic and cardiac disease states. Echocardiography, catheterizatton, and nuclear magnetic resonance techniques are diagnostic tools available to the physician. Early diagnosis and surgical intervention are curative measures for many benign cardiac tumors. Malignant variants are uniformly unresponsive to treatment.
Localization of neuroendocrjne tumors of the pancreas
Authors: Carrasco C. Humberto
Published: February 2007

The diagnosis of neuroendocrine tumors of the pancreas is based on clinical, biochemical, and ultrastructural data. The different radiological modalities are employed only for localization, except in the case of nonftinctioning neoplasms, for which a differential diagnosis from adeno‐carcinoma can be suggested based on the radiographic images. Generally, the initial evaluation should consist of the noninvasive studies and should be complemented by angiography and, in cases of functioning neoplasms, with pancreatic venous sampling if the preliminary findings are inconclusive. However, the localizing work‐up should be terminated when the information obtained is sufficient to determine the therapy that will follow. If the ultrasonic or computed tomographic findings preclude surgical resection, further work‐up is obviously unnecessary.
Photosensitization of malignant tumors
Authors: Dougherty Thomas J.
Published: February 2007

Photodynamic therapy is a new, experimental method of treating malignant tumors by utilizing the relatively selective retention of the photosen‐sitizer (hematoporphyrin derivative or dihematoporphyrin ether) and its ability to elicit an efficient photodynamic reaction upon activation with penetrating viable light. Application of this therapy to tumors in the bronchus, bladder, skin, and several other sites has demonstrated both safety and efficacy, even in advanced cases. Eradication of early stage tumors in the bronchus and bladder has been demonstrated. Selective retention of the photosensitizers in tumors is apparently related to the relatively large size of the aggregates of these materials causing phagocytosis by reticuloendothelial cells as well as preventing rapid clearance from tumor interstitial fluid and subsequent uptake in lipophylic components of cells. Upon light activation, generally delivered from lasers via fiber optics, the sensitizers generate singlet oxygen, the apparent cytotoxic agent, causing both vascular damage and injury to tumor cells.
The changing role of surgery in the treatment of primary liver cancer
Authors: Tang Zhao‐You , Yu Ye‐Qin , Zhou Xin‐Da
Published: February 2007

For decades, the role of surgery in the treatment of primary liver cancer (PLC) was important but limited. However, a comparison of pathologically proven PLC during the three periods 1958–1966, 1967–1975, and 1976–1984 revealed that as a result of alpha fetoprotein (AFP) serosurvey, changing concepts in surgical oncology, and introduction of new surgical modalities, the role of surgery has become greater. The increasing proportion of subclinical PLC (0, 7.2, and 21.2%) has favored the increasing series resection rate (16.1, 34.7, and 39.6%) and palliative surgery (13.7, 17.0, and 29.8%). The results indicated that early resection, reoperation for subclinical recurrence, resection of huge PLC in stages, and combination of palliative surgery other than resection might be responsible for the increasing 5‐year survival rate (1.7, 7.1, and 19.5%) in the entire series.
Minute lesions of esophageal cancer
Authors: Endo Mitsuo , Takemoto Tadayoshi , Shirakabe Hikoo
Published: February 2007

Fifty‐four cases of minute esophageal cancer (1 cm or less in the greatest dimension) were collected and analyzed. Of these 67% were mucosal cancer and 28% were submucosal cancer. Prognosis was anticipated to be good as there was only one case of lymph node metastasis and three of vascular invasion. A lesion of 1 cm can be regarded as curable regardless of its depth of invasion. The endoscopic approach with use of a dye staining technique is useful for detection of or screening for minute esophageal cancer.
Endoscopic laser treatment of superficial esophageal cancer
Authors: Fujimaki Masao , Nakayama Komei
Published: February 2007

Recently, lasers are being increasingly applied in die treatment of cancers of various organs, including the esophagus. In the present multiinstitu‐tional series, two lesions in two cases were successfully treated with die high‐energy Nd‐YAG laser and 15 lesions in 14 cases were treated with the low‐energy argon dye laser following photosensitization with hemato‐porphyrin derivative. Although satisfactory results were obtained in most cases, it was concluded that the equipment and photosensitizer require improvements.