bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of locally advanced/unresectable rectal cancer
Authors: Minsky Bruce D. 
Published: February 2007

AbstractThe standard treatment for locally advanced/unresectable rectal cancer is preoperative radiation therapy followed by surgery. The primary goals of the preoperative treatment are to convert the cancer to a resectable status and to decrease the incidence of local failure. Phase I/II non‐randomized data suggest that the most effective treatment is preoperative combined modality therapy followed by maximal surgical resection and intraoperative radiation therapy. In patients who cannot receive preoperative therapy, the use of maximal surgical resection plus intraoperative radiation therapy may be of benefit, however, it remains investigational. © 1995 Wiley‐Liss, Inc.
Toxicity associated with boronophenylalanine and cranial neutron irradiation
Authors: Cano William G. , Solares Guido R. , Dipetrillo Thomas A. , Meylaerts Sven A. G. , Lin Shan C. , Zamenhof Robert G. , Saris Stephen C. , Duker Jay S. , Goad Elizabeth , Madoc‐Jones Hywel , Wazer David E. 
Published: February 2007

AbstractBoron neutron capture therapy (BNCT) involves administration of a tumor selective boron compound followed by neutron irradiation directed at the target organ. Several studies have shown antitumor activity in animal models with BNCT using the amino acid analog boronophenylalanine (BPA). This study investigates the pharmacological toxicity of BPA in rabbits and the acute (14 days) and subacute (100 days) radiotoxicity of cranial BNCT with BPA in normal mice. To assess the toxicity of BPA alone the drug was administered orally in either a single dose of 5,000 mg/kg or 5 divided doses of 1,000 mg/kg/day to rabbits which were subsequently sacrificed at 2.5 or 4.5 weeks. To study the radiotoxic effects of BNCT mice were given BPA orally followed by cranial irradiation with a thermal neutron beam 3 hr later, with resulting brain doses ranging from 1,100 to 2,750 cGy‐Eq [compound‐relative biological effectiveness (C‐RBE) of 1.3 for 10B, 3.2 for neutrons, and 1.0 for gammas]. Mice were sacrificed 14 or 100 days after irradiation to study acute and subacute radiation toxicity, respectively. BPA alone demonstrated no discernible toxicity at the doses and schedules administered. BNCT resulted in a dose‐independent acute dilatation of the cerebral ventricles and mild cerebral atrophy. No neurologic deterioration could be detected in animals exposed to 2,200 cGy‐Eq or lower but acute clinical morbidity was evident at 2,750 cGy‐Eq, possibly related to non‐neural toxicity. Mice exposed to a dose of 2,750 cGy‐Eq to the brain also presented with moderately severe gastrointestinal toxicity consisting of epithelial hyperplasia or atrophy and necrosis. Animals exposed to lower doses showed no significant gastrointestinal radiotoxicity. All animals sacrificed at 100 days that received 2,200 cGy‐Eq developed bilateral posterior subcapsular cataracts. Lower doses had a minimal ocular toxic effect. It is concluded that there was no discernible toxicity from BPA administration at daily doses 10 times higher than those required for proposed therapeutic applications. Single‐fraction BNCT irradiations to the head showed significant ocular toxicity with a threshold between 1,650 and 2,200 cGy‐Eq; gastrointestinal toxicity with a threshold between 2,200 and 2,750 cGy‐Eq; and neural toxicity with a threshold ≦l,100 cGy‐Eq for histopathologic lesions. © 1995 Wiley‐Liss, Inc.
Utilization of 125I monoclonal antibody in the management of primary glioblastoma multiforme
Authors: Miyamoto Curtis , Brady Luther W. , Rackover Michael , Emrich Jacqueline , Class Reiner , Bender Hans , Dadparvar Simin , Woo David , Young Timothy , Eshleman Jeffrey , Dilling Thomas , Micaily Bizhan , Steplewski Zenon , Koprowski Hilary , Black Perry , Nair Somnath , McCormack Thomas 
Published: February 2007

AbstractThe objective of this study was to assess the toxicity and potential efficacy of the adjuvant administration of an iodine 125 (125I)‐labeled monoclonal antibody 425 for primary glioblastoma multiforme. From January 29, 1987, to October 1, 1993, 60 patients with a diagnosis of glioblastoma multiforme received an average of three intravenous or intraarterial injections of 125I‐labeled antiepidermal growth factor receptor monoclonal antibody (1251425). All patients had biopsy or resection followed by postoperative radiation therapy. Patients were included who had either stereotactic irradiation or brachytherapy (5 patients), or who were not candidates for these treatments. Stratification was made by Karnofsky performance status (KPS) and age. Treatments were administered on an outpatient basis. The mean KPS was 78, and the total cumulative dose of 125I 425 was approximately 150 mCi. Among this entire group were 6 patients who received 10–80 mg of unlabeled “blocking” 425 to block binding sites on non‐tumor cells prior to the second intravenous infusion of 125I 425. No patients were excluded from the statistical analysis. The median actuarial survival for all patients treated adjuvantly for glioblastoma multiforme was 13 months. Both age and KPS correlated positively with survival, as would be expected. The toxicity from the administration of repeated doses of 125I 425 was low. No patient had chronic toxicity attributed to the monoclonal antibody therapy. Acute toxicity was observed in 1 patient who received a single dose >60 mCi. We conclude that the repeated administration of 1251425 is safe and may have some benefit in the management of primary glioblastoma multiforme. This may be especially true for patients who do not qualify for other forms of more aggressive management. A prospective randomized trial should be performed. © 1995 Wiley‐Liss, Inc.
Response predictors for high‐grade gliomas given definitive irradiation
Authors: Shaeffer James , Zhu An , Leslie Susan , Kolm Paul , El‐Mahdi Anas M. 
Published: February 2007

AbstractThe prognostic significance of the following 9 variables was assessed using archival specimens from a series of patients with high‐grade astrocytic gliomas treated definitively with irradiation: histologic grade, patient age, tumor nuclear roundness factor (TNRF), tumor nuclear area (TNA), mitotic index, cell density, necrosis, giant cells, and pseudopalisading cells (PPC). Using univariate analysis, 7 of the 9 variables were significantly related to overall survival: patient age (P < 0.0001), mitotic index (P < 0.0001), cell density (P = 0.0004), histologic grade (P = 0.0005), necrosis (P =0.0042), PPC (P = 0.0016), and TNRF (P = 0.0232). When adjusted for age, 4 variables were significantly related to overall survival: histologic grade, mitotic index, cell density, and TNRF. When adjusted for both age and grade, 3 previously significant variables (mitotic index, cell density, and TNRF) were no longer significant, indicating possible redundancy with grade. When each variable was adjusted for every other variable, only age remained independently and significantly (P = 0.0022) predictive for overall survival. None of the 9 variables was significantly related to disease‐free survival. © 1995 Wiley‐Liss, Inc.
Three‐dimensional external‐beam radiation treatment planning and real‐time dose verification of pituitary adenoma: Clinical and physical considerations
Authors: Ahmad M. , Fontenla D. P. , Lai P. P. , Del Rowe J. , Yaparpalvi R. , Deore S. M. , Curran J. , Wojcicka J. , Vikram B. 
Published: February 2007

AbstractThe purpose of this study is to establish protocols for simulation and external‐beam radiotherapy of pituitary tumors and to examine the performance of a new 3‐dimensional treatment planning system (3‐D RTP). The asymmetric collimation feature of a dual‐energy photon beam linear accelerator allows the user to set up half‐beam treatment fields posterior to the orbits with no divergence to anterior structures.Treatment planning was performed with a relatively new Food and Drug Adminisration (FDA)‐approved 3‐D RTP system. Computerized tomographic (CT) scans used by this system to generate isodose distributions and dose‐volume histograms were obtained directly from the scanner which is connected via ethernet cabling to the 3D treatment planning system. These were used for evaluating the dose distribution to the treatment volume, clinical target volume, gross tumor volume, and certain critical organs. Using 6 and 18 MV photon beams, different configurations of standard treatment techniques for pituitary tumors, i.e., a 190° flying wedge arc, 3‐fields (an anterior plus a lateral wedged pair), and a pair of lateral fields, were studied and the resulting dose distributions were analyzed. Real‐time dose measurements on patients using diode dosimetry were made and compared with computed dose values.With regard to minimizing radiation dose to surrounding structures, (i.e., lens, temporal lobes, spinal cord, etc.) the 190° flying wedge arc technique gave the best isodose distributions, followed by 3 fields (an anterior plus a lateral wedged pair). The opposing lateral fields gave the highest integral dose to the temporal lobes. The dose measured on the patient during the treatment agrees to within ±2% with the computed dose.The protocols presented in this work for simulation, immobilization, and treatment planning of patients with pituitary tumors provide the optimum dose distributions in the target volume with reduced irradiation of surrounding non‐target tissues, and can be easily implemented in a radiation oncology department. The presence of a real‐time dose‐measuring system plays an important role in verifying the actual delivery of radiation dose. © 1995 Wiley‐Liss, Inc.
Localized subclinical radiation enteropathy prolongs intestinal transit time: An experimental study in a rat model
Authors: Hauer‐Jensen Martin , Theus John W. , Bradley Jeffrey D. , Baker Max L. , Langberg C. W. 
Published: February 2007

AbstractIntestinal dysmotility is a prominent feature of chronic radiation enteropathy. This study addressed the question whether localized radiation enteropathy without anatomical obstruction influences stomach to cecum transit time. Male rats were orchiectomized and a loop of ileum was sutured to the inside of the scrotum. After 3 weeks postoperative recovery, the “scrotal hernia” containing the transposed intestine was irradiated with 18 twice‐daily fractions of 2.8 Gy, or 9 daily fractions of 5.6 Gy orthovoltage X‐rays. Control animals were operated and sham‐irradiated. Stomach to cecum transit time was assessed 26 weeks after irradiation. A 1‐ml bolus of barium suspension was administered by gavage and diagnostic X‐ray films were obtained at 0,1, 2,2.5, 3, 3.5, and 4 hr. Transit time was defined as the time to the first X‐ray that showed unequivocal contrast filling of the cecum. Normal range and day‐to‐day variability were assessed in normal, unoperated control rats. After completion of transit studies, the rats were euthanized, samples from shielded and irradiated intestine were procured, and radiation injury was assessed with a histopathological scoring system. Median stomach to cecum transit time in unoperated controls was 2.25 hr. The surgical procedure and aging did not significantly affect transit time. Transit time was significantly prolonged both in the 2.8 Gy × 18 group (P = 0.02) and in the 5.6 Gy × 9 group (P = 0.0001). The association between histopathologic radiation injury and transit time did not reach statistical significance. We conclude that non‐obstructing radiation injury in the distal ileum significantly prolongs intestinal transit time and that small bowel follow‐through with barium contrast may be used to assess radiation enteropathy in this animal model. © 1995 Wiley‐Liss, Inc.
Treatment decisions in elderly breast cancer patients
Authors: Konski Andre , Marsa Gerald , Mueller William , Cobau Charles , Horvath William , Zeidner Steven , Schaefer Paul , Shaikh Bahu , Mali John , Smith Mary , Eggleston William 
Published: February 2007

AbstractThe purpose of this study was to investigate the patterns of care in women over the age of 65 years presenting with breast cancer. Tumor registry data from three different sized and geographically located hospitals in northwest Ohio were reviewed and analyzed. Three hundred forty‐five patients were eligible for analysis. An age difference was noted between those patients receiving lumpectomy only compared to those patients receiving mastectomy or lumpectomy and radiation. The majority of patients with regional disease received hormonal therapy. Only two of six patients with positive lumpectomy margins experienced a local recurrence. The tumor volume was statistically significantly higher in patients who experienced a local recurrence. In conclusion, treatment for elderly patients with breast cancer should be based on physiologic not chronologic age. © 1995 Wiley‐Liss, Inc.
Prostate brachytherapy: Improvements in prostate volume measurements and dose distribution using interactive ultrasound guided implantation and three‐dimensional dosimetry
Authors: Stone Nelson N. , Stock Richard G. , Keith DeWyngaert J. , Tabert Andrea 
Published: February 2007

AbstractImprovements in prostate volume measurements and in dose distribution have led to an increase in the use of brachytherapy for prostate cancer. The addition of interactive ultrasound and three‐dimensional dosimetry has also enhanced the treatment plan. We investigated the effect of these changes on implant outcome in patients with localized carcinoma of the prostate who were treated with these new techniques. Two hundred twenty‐one men with an elevated prostate specific antigen (PSA) or abnormal digital rectal examination (DRE) had transrectal ultrasound evaluation and needle biopsy of the prostate. Prostate volume was determined by ellipsoid and planimetry techniques. Differences of at least 5%, 10%, 15%, 25%, and 50% between the two techniques were found in 170 (77%), 130 (59%), 102 (46%), 53 (24%), and 11 (5%), respectively. In addition, the ellipsoid measurements, which approximate the caliper measurements of the open retropubic implants, were found to underestimate gland volume by 10% in 47 patients (21%), 15% in 39 (18%), 25% in 28 (13%), and 50% in 8 (4%). In 75 patients who had 125I implant the dose to 90% (D90) of the gland increased from 7,619 to 15,806 cGy (P < 0.02) by distributing the majority (70%) of the activity in the periphery and by increasing the total implanted activity by 35%. Despite this peripheral dose placement and increased activity, there was no increase in dose to the anterior rectal wall. We conclude that accurate prostate gland determinations (by planimetry), a peripheral activity distribution, and a 35% increase in implanted activity are necessary in order to ensure adequate dose coverage to the prostate gland when implanting 125I. These changes also may be accomplished without an increase in rectal dose and subsequent radiation proctitis. © 1995 Wiley‐Liss, Inc.
Standardized treatment planning for high dose rate vaginal cuff brachytherapy
Authors: Petereit Daniel G. , Edwards Scott A. , Thomadsen Bruce R. , Fowler Jack F. , Buchler Dolores A. , Kinsella Timothy J. 
Published: February 2007

AbstractThe purpose of this study was to establish the efficacy of standardized treatment planning for high dose rate (HDR) vaginal cuff brachytherapy in order to simplify and shorten the brachytherapy procedure. Two separate but related studies are presented. The first examined the reproducibility of treatment planning by assessing interoperator variability. This provided a baseline assessment of variability to evaluate standardized treatment planning in the second study. The second study examined interpatient variability in which the treatment plans of 20 patients were investigated by two different treatment methods. The first method used the dosimetry of the first insertion for the next insertion, while the other method utilized a standardized plan for all insertions dependent upon ovoid size. The dose was prescribed to the vaginal surface using either applicator points or dose points. Based on multiple calculations, a graph of distance vs. dose was generated to determine the dose to the bladder and rectum for a given implant. In the first study, interoperator variability was acceptable with a standard deviation of 0.4% of the prescribed dose using dose points for the worst case. Applicator points were less reproducible with a worst‐case standard deviation of 2.1% of the prescribed dose. In the second study, implementing initial dosimetric plans for the second implant for an individual patient yielded a worst‐case standard deviation of 2.4% of the prescribed dose. The use of standardized treatment plans for all implants was also efficacious with a worst‐case standard deviation of 1.7% of the prescribed dose. Treatment plans were always more reproducible when calculated to dose points rather than applicator points. Analysis of maximum bladder and rectal doses provided acceptable late tissue doses as predicted by the linear quadratic model. In conclusion, standardized dosimetry plans for vaginal cuff insertion are feasible and reliable in producing precise delivery of vaginal surface doses. The use of dose vs. distance curves facilitates rapid planning by providing a close approximation of the maximum bladder and rectal doses. © 1995 Wiley‐Liss, Inc.
Tumor size does not limit radiation‐inducible gene therapy in a human xenograft model
Authors: Mauceri Helena J. , Hallahan Dennis E. , Lee Henry , Beckett Michael A. , Sukhatme Vikas , Weichselbaum Ralph R. 
Published: February 2007

AbstractTumor size has been reported to be a limiting factor in both radiotherapy (RT) and gene therapy. Therefore, we assessed the effects of tumor necrosis factor‐alpha (TNF‐α) gene therapy and radiation in relatively large tumors in a human xenograft system. We linked DNA sequences from the promoter region of the radiation‐inducible gene Egr‐1 to the cDNA sequence that encodes human TNF‐α, a radiosensitizing cytokine. The Egr‐TNF construct was transfected into the human hematopoietic cell line HL525. Stable transfectants, exhibiting radiation inducibility of TNF‐α in vitro (clone 2 cells), were directly injected into xenografts of a radioresistant human squamous cell carcinoma cell line, SQ‐20B. In a previous study, 100 mm3 tumors treated with radiation and clone 2 cells demonstrated significant tumor control (P < 0.0001) when compared with tumors treated with clone 2 alone or radiation alone. In the present study, 450 mm3 xenografts treated with clone 2 cells and radiation were significantly smaller (P < 0.01) at the nadir of regression than tumors treated with radiation alone. Because the radiation dose was held constant (40 Gy) in both 100 and 450 mm3 xenografts, only one cure was noted in the larger tumors. These data support an interactive anti‐tumor effect in vivo between radiation and TNF‐α gene therapy which is equal in both small and large human tumor xenograft models. © 1995 Wiley‐Liss, Inc.
Mini review: Multistep process of ultraviolet‐induced nonmelanoma skin carcinogenesis
Authors: Bleuel Kerstin , Figueroa Reynel , Härle Cosima , Popp Susanne , Vormwald‐Dogan Vera , Boukamp Petra 
Published: February 2007

AbstractUltraviolet (UV)‐induced nonmelanoma skin cancer requires a number of genetic changes before tumors can develop. To determine the sequence of these changes; we performed a series of functional studies by investigating the spontaneously immortalized human skin keratinocyte HaCaT cell line. We established a multistep in vitro carcinogenesis model that allowed us to place known (mutational inactivation of the tumor suppressor gene p53, ras oncogene activation) and novel (loss of chromosome 3p as carrier of “senescence” gene(s) and chromosome 15 as carrier of a tumor suppressor gene as well as telomerase up‐regulation) genetic alterations involved in the process of skin carcinogenesis in chronological order. © 1995 Wiley‐Liss, Inc.
Use of amphotropic retroviruses expressing human papillomavirus 16 E6 and E7 to determine the consequences of acute expression of the viral oncogenes and to establish immortalized human cell lines
Authors: Galloway D. A. , Halbert C. L. , Demers G. W. , Foster S. A. , Blanton R. A. , Merrick D. , Klingelhutz A. , McDougall J. K. 
Published: February 2007

AbstractWe developed a series of amphotropic retroviruses expressing the E6 and E7 oncogenes from human papillomavirus (HPV) 16 and HPV 6. LXSN16E6E7 efficiently immortalized a wide variety of primary cell types, including epithelia from foreskin, cervix, breast, oral cavity, urogenital region, kidney, prostate, ovary, etc., as well as smooth muscle cells, endothelial cells, fibroblasts, hepatocytes, melanocytes, and others. Rare clones of keratinocytes were established by expression of E7 alone, and breast cells that had bypassed M0 were immortalized by E6 alone. However, in general, efficient immortalization required both E6 and E7 of HPV 16. The immortalized cell lines were nontumorigenic in nude mice and retained many of the differentiated characteristics of the primary cells; however, they invariably had chromosomal abnormalities.Acute expression of E6 or E7 did not alter the doubling time of cells in culture; however, E7 disrupted normal suprabasal quiescence. No increase in aneuploidy or alteration in the rate of telomere shortening was observed before crisis, and cells continued to express markers of epithelial differentiation in organotypic culture. The ability of cells to bypass growth arrest signals was altered by the HPV oncogenes. © 1995 Wiley‐Liss, Inc.
Extended abstract: Abrogation of cell cycle checkpoint control in preneoplastic cells
Authors: Tlsty Thea D. 
Published: February 2007

AbstractGenomic integrity is maintained by a network of cellular activities that assesses the status of the genome at a given point in time and that provides signals to proceed with or to halt cell cycle progression. Recent studies have identified cellular proteins that are the targets for the viral oncoproteins involved in these processes. We demonstrate that the expression of human papilloma virus type 16 E6 and E7 oncoproteins in normal mortal cells disrupts the integration of the network of signals that maintain genomic integrity. © 1995 Wiley‐Liss, Inc.
In vitro multistep human prostate epithelial cell models for studying prostate carcinogenesis
Authors: Rhim J. S. , Peehl D. M. , Webber M. M. , Jay G. , Dritschilo A. 
Published: February 2007

AbstractWe have recently developed in vitro multistep human prostate epithelial (HPE) cell models that are suitable for studying prostate carcinogenesis. We have shown the stepwise immortalization and transformation of adult HPE cells grown in serum‐free medium by a combination of human papilloma virus (HPV)‐18 and v‐Ki‐ras. These observations are consistent with molecular studies on human prostate adenocarcinomas that suggest that both the activated ras gene and HPVs play a role in prostate carcinogenesis. We also established adult HPE cells grown in serum‐free medium and immortalized by Polybrene‐induced DNA transfection with a plasmid containing an origin‐defective SV40 genome. The subsequent addition of v‐Ki‐ras gene to these cells induced morphological alteration and tumors when they were transplanted into nude mice. In addition, we have achieved the neoplastic conversion of a nontumorigenic SV40‐immortalized fetal HPE line by v‐Ki‐ras gene. These cell lines should be useful in defining the multistep mechanisms of carcinogenesis of the prostate. © 1995 Wiley‐Liss, Inc.